Search results for: anti-inflammatory cytokines

Authors: Włodzimierz Lewandowski, Renata Świsłocka, Aleksandra Golonko, Grzegorz Świderski, Monika Kalinowska

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Caffeic acid (3,4-dihydroxycinnamic) is distributed in a free form or as ester conjugates in many fruits, vegetables and seasonings including plants used for medical purpose. Caffeic acid is present in propolis – a substance with exceptional healing properties used in natural medicine since ancient times. The antioxidant, antibacterial, antiinflammatory and anticarcinogenic properties of caffeic acid are widely described in the literature. The biological activity of chemical compounds can be modified by the synthesis of their derivatives or metal complexes. The structure of the compounds determines their biological properties. This work is a continuation of the broader topic concerning the investigation of the correlation between the electronic charge distribution and biological (anticancer and antioxidant) activity of the chosen phenolic acids and their metal complexes. In the framework of this study the synthesis of new metal complexes of sodium, magnesium, aluminium, iron (III) ruthenium (III) and osmium (III) with caffeic acid was performed. The spectroscopic properties of these compounds were studied by means of FT-IR, FT-Raman, UV-Vis, ¹H and ¹³C NMR. The quantum-chemical calculations (at B3LYP/LAN L2DZ level) of caffeic acid and selected complexes were done. Moreover the antioxidant properties of synthesized complexes were studied in relation to selected stable radicals (method of reduction of DPPH and method of reduction of ABTS). On the basis of the differences in the number, intensity and locations of the bands from the IR, Raman, UV/Vis and NMR spectra of caffeic acid and its metal complexes the effect of metal cations on the electronic system of ligand was discussed. The geometry, theoretical spectra and electronic charge distribution were calculated by the use of Gaussian 09 programme. The geometric aromaticity indices (Aj – normalized function of the variance in bond lengths; BAC - bond alternation coefficient; HOMA – harmonic oscillator model of aromaticity and I₆ – Bird’s index) were calculated and the changes in the aromaticity of caffeic acid and its complexes was discussed. This work was financially supported by National Science Centre, Poland, under the research project number 2014/13/B/NZ7/02-352.

Keywords: antioxidant properties, caffeic acid, metal complexes, spectroscopic methods

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Authors: Ayu S. Muhamad, Michael Gleeson

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Immunomodulators are substances that alter immune system via dynamic regulation of messenger molecules. It can be divided into immunostimulant and immunosuppressant. It can help to increase immunity of people with a low immune system, and also can help to normalize an overactive immune system. Aim of this study is to investigate the effects of in vitro exposure to low and high doses of several immunomodulators which include caffeine, kaloba and quercetin on antigen-stimulated whole blood culture cytokine production. Whole blood samples were taken from 5 healthy males (age: 32 ± 12 years; weight: 75.7 ± 6.1 kg; BMI: 24.3 ± 1.5 kg/m2) following an overnight fast with no vigorous activity during the preceding 24 h. The whole blood was then stimulated with 50 µl of 100 x diluted Pediacel vaccine and low or high dose of immunomodulators in the culture plate. After 20 h incubation (5% CO2, 37°C), it was analysed using the Evidence Investigator to determine the production of cytokines including IL-2, IL-4, IL-10, IFN-γ, and IL-1α. Caffeine and quercetin showed a tendency towards decrease cytokine production as the doses were increased. On the other hand, an upward trend was evident with kaloba, where a high dose of kaloba seemed to increase the cytokine production. In conclusion, we found that caffeine and quercetin have potential as immunosuppressant and kaloba as immunostimulant.

Keywords: caffeine, cytokine, immunomodulators, kaloba, quercetin

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Authors: Mohamed A. Dkhil, Denis Delic, Saleh Al-Quraishy

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Coccidiosis causes considerable economic loss in the poultry industry. The current study aimed to investigate the response of goblet cells as well as the induced tissue damage during Eimeria papilata infection. Mice were infected with sporulated E. papillata oocyts. On day 5 post-infection, the fecal output was determined. Also, the jejunum was prepared for the histological, histochemical and molecular studies. Our results revealed that the intestinal coccidian infection with E. papillata induced a marked goblet cell hypoplasia and depleted mucus secretion. Also, the infection was able to alter the jejuna architecture and increased the apoptotic cells inside the villi. In addition, the real time PCR results indicated that, the inflammatory cytokines TNF-α, iNOS, IFN-y and IL-1β were significantly up-regulated. In contrast, the mRNA expression patterns of IL-6 in response to E. papillata infection did not differ significantly between control and infected mice. Moreover, the mRNA expression of TLR4 was significantly up-regulated, whereas the expression of MUC2 is significantly down-regulated upon infection. Further studies are required to understand the regulatory mechanisms of goblet cells related genes.

Keywords: goblet cells, Eimeria papillata, mice, jejunum

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Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi

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Crohn’s disease (CD) is a chronic gastrointestinal segment inflammation encompassing immune dysregulation in a genetically susceptible individual in response to the environmental triggers and interaction between the microbiome and immune system. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures and enteric fistulae. Increased production of Th1 and Th17-cell cytokines and defects in T-regulatory cells have been associated with CD. Th17-cells are essential for protection against extracellular pathogens, but their atypical activity can cause autoimmunity. Intrinsic defects in the control of programmed cell death in the mucosal T-cell compartment are strongly implicated in the pathogenesis of CD. The apoptosis defect in mucosal T-cells in CD has been endorsed as an imbalance of the Bcl-2 and the Bax. The immune system encounters foreign antigens through microbial colonization of mucosal surfaces or infections. In addition, FOSL downregulated IL-26 expression, a cytokine that marks inflammatory Th17-populations in patients suffering from CD. Furthermore, the expression of IL-23 is associated with the transcription factor primary leucine zipper transcription factor ATF-like (Batf). Batf-deficiency demonstrated the crucial role of Batf in colitis development. Batf and IL-23 mediate their effects by inducing IL-6 production. Strong association of IL-23R, Stat3, and Stat4 with IBD susceptibility point to a critical involvement of T-cells. IL-23R levels in transfer fistula were dependent on the AP-1 transcription factor JunB that additionally controlled levels of RORγt by facilitating DNA binding of Batf. T lymphocytes lacking JunB failed to induce IL-23- and Th17-mediated experimental colitis highlighting the relevance of JunB for the IL-23/ Th17 pathway. The absence of T-bet causes unrestrained Th17-cell differentiation. T-cells are central parts of immune-mediated colon fistula. Especially Th17-cells were highly prevalent in inflamed IBD tissues, as RORγt is effective in preventing colitis. Intraepithelial lymphocytes (IEL) contain unique T-cell subsets, including cells expressing RORγt. Increased activated Th17 and decreased T-regulatory cells in inflamed intestinal tissues had been seen. T-cells differentiate in response to many cytokines, including IL-1β, IL-6, IL-23, and TGF-β, into Th17-cells, a process which is critically dependent on the Batf. IL-23 promotes Th17-cell in the colon. Batf manages the generation of IL-23 induced IL-23R+ Th17-cells. Batf is necessary for TGF-β/IL-6-induced Th17-polarization. Batf-expressing T-cells are the core of T-cell-mediated colitis. The human-specific parts of three AP-1 transcription factors, FOSL1, FOSL2, and BATF, are essential during the early stages of Th17 differentiation. BATF supports the Th17 lineage. FOSL1, FOSL2, and BATF make possession of regulatory loci of genes in the Th17 lineage cascade. The AP1 transcription factor Batf is identified to control intestinal inflammation and seems to regulate pathways within lymphocytes, which could theoretically control the expression of several genes. It shows central regulatory properties over Th17-cell development and is intensely upregulated within IBD-affected tissues. Here, we demonstrated that targeting Batf in IBD appears as a therapeutic approach that reduces colitogenic T-cell activities during fistula formation while aiming to affect inflammation in the gut epithelial cells.

Keywords: immune system, Crohn’s Disease, BATF, T helper cells, Bcl, interleukin, FOSL

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Authors: Laleh Behboudi Tabrizi, Melika Naserzare

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Accumulating experimental and epidemiologic data smoker individuals are more prone to systemic inflammation than non-smokers. In this study we aimed to determine serum TNF-α and C-reactive protein (CRP) as pro-inflammatory cytokines in response to 3 months aerobic training in smoker men. A total 30 middle-aged healthy smokers selected for participate in this study and were divided into either control or exercise groups. The subjects in exercise group were completed a 3 months aerobic training program for 3 sessions per week at 60 – 80 % of maximal heart rate. Those in control group did nit participated in exercise training. Pre and post-training of CRP and TNF-α were measured in two groups. Student’s t-tests for paired samples were performed to determine whether there were signigcant within-group changes in the outcomes. P value of <0.05 was accepted as significant. No significant differences were found in anthropometrical and biochemical markers between two groups at baseline. Aerobic training program resulted in a significant decrease in anthropometrical markers and serum TNF-α but not in serum CRP in exercise group. All variables remained without changes in control groups. Based on these finding, it is concluded that aerobic training can be improve inflammatory cytokine with emphasis on TNF-α in smokers.

Keywords: cigarette, cytokine, chronic training, inflammation

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Authors: Hani M. M. Alothaid, Louise Robson, Richmond Muimo

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This study will investigate cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) dependent calcineurin (Cn), known as protein phosphatase 2 B (PP2B) as well, regulation of chloride ion (Cl⁻) secretion and the release of pro-inflammatory molecules in immune cells such as cytokines. THP-1-derived monocytes, primary human monocytes and the bronchial epithelial cell line (16HBE14o-) were used in this study. The 16HBE14o- cells were chosen as positive control. Hence, to further confirm the expression of cystic fibrosis transmembrane conductance regulator (CFTR), calcium binding protein (S100A10), annexin A2 (AnxA2) and calcineurin A subunit (CnA) in all three cell types, cell lysate was probed against corresponding primary antibodies by immunoblotting. Western blot analyses show the expression of CFTR, AnxA2, CnA and S100A10 in THP-1-derived monocytes and primary human monocytes. In conclusion, CFTR, S100A10, CnA and AnxA2 are expressed in THP-1-derived monocytes and primary human monocytes and regulate Cl⁻ secretion. Also, they may play a role in the pro-inflammatory molecules release. The ongoing work will confirm interaction between these proteins in the cell lines.

Keywords: annexin A2, calcineurin, CFTR, chloride, monocytes, pro-inflammatory molecules, S100A10

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Authors: Hae Jeong Park, Joo-Ho Chung

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In this study, the effect of essential oil from Chamaecyparis obtuse (EOCO) on early life stress using maternal separation (MS) rats was investigated. Anxiety-related behaviors were examined in MS rats using the elevated plus-maze (EPM) test. The changes of gene expressions by EOCO in the hippocampus of MS rats were analyzed using a microarray method. Rats in the MS groups were separated from their respective mothers from postnatal day (pnd) 14 to 28. Rats in the EOCO-treated groups were exposed to EOCO for 1 h or 2 h by inhalation from pnd 21 to 28. The EOCO-treated MS rats showed decreased anxiety-related behaviors compared to the MS rats in the EPM test. In the microarray analysis, EOCO downregulated the expressions of cytokine genes such as Ccl2, Il6, Cxcl10, Ccl19, and Il1rl in the hippocampus of MS rats, and it was also confirmed through RT-PCR. In particular, the expressions of Ccl2 and Il6 were predominantly decreased by EOCO in the hippocampus of MS rats. Interestingly, their protein expressions were also reduced by EOCO in MS rats. These results indicate that EOCO decreases MS-induced anxiety-related behaviors, and modulate cytokines, particularly Ccl2 and Il6, in the hippocampus of MS rats.

Keywords: anxiety-related behavior, Chamaecyparis obtuse, cytokine gene, early-life stress, maternal separation

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Authors: Sadaf Ilyas

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Recombinant cytokines have been employed successfully as potential therapeutic agent. Some cytokine therapies are already used as a part of clinical practice, ranging from early exploratory trials to well established therapies that have already received approval. Interleukin 15 is a pleiotropic cytokine having multiple roles in peripheral innate and adaptive immune cell function. It regulates the activation, proliferation and maturation of NK cells, T-cells, monocytes/macrophages and granulocytes, and the interactions between them thus acting as a bridge between innate and adaptive immune responses. Unraveling the biology of IL-15 has revealed some interesting surprises that may point toward some of the first therapeutic applications for this cytokine. In this study, the human interleukin 15 gene was isolated, amplified and ligated to a TA vector which was then transfected to a bacterial host, E. coli Top10F’. The sequence of cloned gene was confirmed and it showed 100% homology with the reported sequence. The confirmed gene was then subcloned in pET Expression system to study the IPTG induced expression of IL-15 gene. Positive expression was obtained for number of clones that showed 15 kd band of IL-15 in SDS-PAGE analysis, indicating the successful strain development that can be studied further to assess the potential therapeutic intervention of this cytokine in relevance to human diseases.

Keywords: Interleukin 15, pET expression system, immune therapy, protein purification

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Authors: Connick K, Lalor R, Murphy A, O’Neill S. M., Rabab S. Zalat, Eman E. El Shanawany

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Cryptosporidium parvum is an opportunistic intracellular parasite that causes mild to severe diarrhea in human and animal populations and is an important zoonotic disease globally. In immunocompromised hosts, infection Canbe life-threatening as no effective treatments are currently available to control infection. To increase our understanding of the mechanisms that play a role in host-parasite interactions at the level of the immune response, we investigated the effects of Cryptosporidium parvum antigen (CPA) on bone marrow-derived (DCS). Herein we examined cytokine secretion and cell surface marker expression on DCs exposed to CPA. We also measured cytokine production in CD4+ cells co-cultured with CPA primed DCs in the presence of anti-CD3. CPA induced a significant increase in the production of interleukin(IL)-12p40, IL-10, IL-6, and TNF-α by DCs and enhanced the expression of the cell surface markers TLR4, CD80, CD86, and MHC11. CPA primed DC co-cultured in the presence of anti-CD3 with CD4+ T-cells inhibited the secretion of Th2 associated cytokines, notably IL-5 and IL-13, with no effects on the secretions of interferon (IFN)-γ, IL-2, IL-17, and IL-10. These findings support studies in the literature that CPA can induce the full maturation of DCs that subsequently initiate Th1 immune responses critical to the resolution of C. parvum infection.

Keywords: cryptosporidium parvum, dendritic cells, IL-12 p70, cell surface marker

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Authors: Urarat Nanna, Jarinyaporn Naowaboot

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Tiliacora triandra (T. triandra) is traditional Southeast Asian medicine and widely used in the cuisines of northeast Thailand and Laos. It has been used as antipyretic, detoxication agent, antiinflammation. But the activity of T. triandra leaf water extract (TTW) in the regulation of metabolic syndrome is still little known. In this study, we evaluated the effects of TTW in high-fat diet (HFD)-induced obese mice. Male ICR mice were induced to be obese by HFD feeding (45 kcal% lard fat) for 12 weeks. During the last 6 weeks of diet feeding, the obese mice were treated with TTW at 250 and 500 mg/kg/day. The biochemical parameters and histology analysis were measured at the end of treatment period. After 6 weeks of TTW treatment, the hyperglycemia, hyperinsulinemia, hyperleptinemia and hyperlipidemia were significantly decreased. Hepatic lipid accumulation and adipocyte hypertrophy were also reduced. Serum adiponectin was increased in TTW-treated obese mice. TTW treatment could reduce the malondialdehyde in serum and liver tissue. Furthermore, the elevated serum inflammatory cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 were reduced (MCP-1) by TTW. These results suggest that T. triandra leaf is a beneficial plant in alleviating hyperglycemia, hyperlipidemia, oxidative stress and inflammation in the obese condition induced by HFD.

Keywords: Tiliacora triandra, insulin resistance, hyperlipidemia, oxidative stress

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Authors: Dzatur Rizqi Fathienah Syarifuddin, Isharyah Sunarno, Eddy Hartono, Siti Maisuri T. Chalid

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Introduction: The potential impact of coronavirus disease 2019 (COVID-19) on the health of expectant mothers and fetuses has strained attention. Pregnant women are considered a vulnerable category to respiratory infections. Moreover, several inflammatory cytokines are 2-100 times more abundant in COVID-19 with cytokine storms than in normal individuals; interleukin 6 (IL-6) exhibits much higher elevations. Investigating potential relationships between IL-6 serum levels and the severity of COVID-19 symptoms in pregnant women is the aim of this study. Material and Methods: Sixty-two eligible pregnant women were divided into a positive COVID-19 group (n=31) and a negative COVID-19 group (n=31) in this cross-sectional study. The research subjects were selected using consecutive sampling. The IL-6 was measured from a vein blood specimen using ELISA methods. Results: The COVID-19 positive group had a higher median IL-6 serum level (45.35 (35.15- 153.99) vs. 38.86 ± 11.43 (15.02-59.52), p=0.03) than the negative group. On the other hand, the IL-6 serum level had comparable value according to the COVID-19 symptoms severity (88.35 ± 36.14 ng/mL vs. 51.09 ± 25.48 ng/mL vs. 56.02 ± 33.20 ng/mL in moderate symptoms, mild symptoms, and asymptomatic, respectively; p=0.152). Conclusion: Although the IL-6 serum levels are not related to COVID-19 symptoms severity, an elevated of this biomarker was found in pregnant women with affected diagnoses.

Keywords: interleukin-6, pregnancy, COVID-19, several inflammatory

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Authors: Bilal Ahmad

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Alzheimer’s disease (AD) is one of the most common neurodegenerative illnesses. However, how Gut-microbiota plays a role in the pathogenesis of AD is not well elucidated. The purpose of this literature review is to summarize and understand the current findings that may elucidate the gut microbiota's role in the development of AD. Methods: A literature review of all the relevant papers known to the author was conducted. Relevant articles, abstracts and research papers were collected from well-accepted web sources like PubMed, PMC, and Google Scholar. Results: Recent studies have shown that Gut-microbiota has an important role in the progression of AD via Gut-Microbiota-Brain Axis. The onset of AD supports the ‘Hygiene Hypothesis’, which shows that AD might begin in the Gut, causing dysbiosis, which interferes with the intestinal barrier by releasing pro-inflammatory cytokines and making its way up to the brain via the blood-brain barrier (BBB). Molecular mechanisms lipopolysaccharides and serotonin kynurenine (tryptophan) pathways have a direct association with inflammation, the immune system, neurodegeneration, and AD. Conclusion: The studies helped to analyze the molecular basis of AD, other neurological conditions like depression, autism, and Parkinson's disease and how they are linked to Gut-microbiota. Further, studies to explore the therapeutic effects of probiotics in AD and cognitive enhancement should be warranted to provide significant clinical and practical value.

Keywords: gut-microbiota, Alzheimer’s disease, second brain aging, lipopolysaccharides, short-chain fatty acids

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Authors: Arghavan Tonkaboni, Shamsolmolouk Najafi, Mohmmad Taghi Kiani, Mehrzad Gholampour, Touraj Goli

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Introduction: Recurrent aphthous stomatitis (RAS) is a multifactorial recurrent oral lesion; which is an autoimmune disease. TH1 cytokines are the most important etiological factors. Autoimmune thyroid disease (ATD) is one of the most common autoimmune diseases and generally coexists with other autoimmune diseases. This study assessed the prevalence of thyroid disease in patients with recurrent aphthous stomatitis. Materials and Methods: This case control study assessed 100 known RAS patients who were diagnosed clinically by oral medicine specialists; venous blood samples were analyzed for thyroid stimulating hormone (TSH), free triiodothyronine (fT3), total thyroxine (fT4), thyroglobulin, anti-thyroid peroxidase antibody (anti-TPO) and anti-thyroglobulin antibody (anti-TG) levels. Results: Fifty patients with RAS aged between 18-42 years (28.5±5.8) and 50 healthy volunteers aged 19-45 years (27.3±5.4) participated. In RAS patients, fT3 and TSH levels were significantly higher (P=0.031, P=0.706); however, fT4 level was lower in the RAS group (P=0.447). Anti TG and anti-TPO levels were significantly higher in the RAS group (P=0.008, P=0.067). Conclusion: Our study showed that ATD prevalence was significantly higher in RAS patients. Based on this study, we recommend assessment of thyroid hormones and antibodies in RAS patients.

Keywords: recurrent aphthous stomatitis, thyroid antibodies, thyroid hormone, thyroid autoimmune disease

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Authors: Hilary P. Stevenson, Alexander J. Hayek, Amie Dereczyk

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In this case report, we provide an example of an asymptomatic COVID-19 positive patient who presented with new-onset psychosis with severe paranoid delusions. He was seen in our ED after ingesting isopropyl alcohol which he reported was an attempt to escape presumed attackers, which at the time was logical to the patient. The patient’s family had COVID-19 symptoms that corresponded to those typically observed from the Omicron variant. The patient was treated successfully, within ten days, with Risperdal twice-daily dosing resulting in the resolution of the patient’s delusions and improved insight regarding the events that led to his hospitalization. In this work, we examine possible contributing factors to new-onset psychosis in the context of COVID-19, a phenomenon that is becoming increasingly notable in the literature. One area of importance is the already established inflammatory hypothesis of psychosis in which defects in the innate immune system, which result in its overactivation, may play a role in a typical first-episode psychosis, in addition to subsequent episodes. Given that COVID-19 is known to cause derangements in the innate immune system, such as cytokine storm reactions, this link may be critical in further understanding the etiologies of new-onset COVID-19 psychosis and its risk factors. Also included in this work is a brief review of antipsychotic interventions that have been described in the literature to date for the first episode of COVID-19-related psychosis. This will explore the potential of some antipsychotics to innately diminish the production of pro-inflammatory cytokines, further enhancing their usefulness in COVID-19 first-episode psychosis patients.

Keywords: COVID-19, first break psychosis, inflammatory hypothesis of psychosis, Risperdal

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Human Herpesvirus 6 (HHV-6), and MS is one potential cause that is not well understood. In this study, we aim to summarize the available data on HHV-6 infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", " Human Herpesvirus 6 ", and "central nervous system" in the databases PubMed and Google Scholar between 2017 and 2022 were searched, and 12 articles were chosen, studied, and analyzed. Results: HHV 6 tends towards TCD 4+ lymphocytes and enters the CNS due to the weakening of the blood-brain barrier due to inflammatory damage. Following the observation that the HHV-6 U24 protein has a seven amino acid sequence with myelin basic protein, which is one of the main components of the myelin sheath, it could cause a molecular mimicry mechanism followed by cross-reactivity. Reactivation of HHV-6 in the CNS can cause the release of proinflammatory cytokines, including TNF-α, leading to immune-mediated demyelination in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HHV-6 and MS, and that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of HHV-6 may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human herpesvirus 6, central nervous system, autoimmunity

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Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig

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Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.

Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)

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Authors: Ferreira RC, Simons HZ, Thompson WS, Cutler AJ, Dopico XC, Smyth DJ, Mashar M, Schuilenburg H, Walker NM, Dunger DB, Wallace C, Todd JA, Wicker LS, Pekalski ML

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Type 1 diabetes is caused by autoimmune destruction of insulin-secreting beta cells in the pancreas. T cells are known to play an important role in this immune-mediated destruction; however, there is no general consensus regarding alterations in cytokine production or T cell subsets in peripheral blood of patients with type 1 diabetes. Using polychromatic flow cytometry of peripheral blood mononuclear cells (PBMCs), we assessed production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 by memory CD4 T effector (Teff) cells in 69 patients with type 1 diabetes and 61 healthy donors. We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). In a separate cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. Consistent with the increased production of IL-21, we also found a 14.9% increase in circulating Tfh cells in the patients with type 1 diabetes (95% CI 2.9, 26.9; p = 0.016). Analysis of IL-21 production by PBMCs from a subset of 46 of the 62 donors immunophenotyped for Tfh showed that frequency of Tfh cells was associated with the frequency of IL-21+ cells (r2 = 0.174, p = 0.004). These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.

Keywords: T follicular helper cell, IL-21, IL-17, type 1 diabetes

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Authors: Jeonghun Lee

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Thyroid-stimulating hormone (TSH) is regulated by the negative feedback of T3 and T4 but is affected by cortisol and cytokines during allostasis. Hence, TSH levels can be influenced by stress through cortisol. In the present study, changes in TSH levels under stress and the potential of TSH as a stress marker were examined in patients lacking T3 or T4 feedback after thyroid surgery. The three stress questionnaires (Korean version of the Daily Stress Inventory, Social Readjustment Rating Scale, and Stress Overload Scale-Short [SOSS]), open-ended question (OQ), and thyroid function tests were performed twice in 106 patients enrolled from January 2019 to October 2020. Statistical analysis was performed using the generalized linear mixed effect model (GLMM) in R software version 4.1.0. In a multiple LMM involving 106 patients, T3, T4, SOSS (category), open-ended questions, the extent of thyroidectomy, and preoperative TSH were significantly correlated with lnTSH. T3 and T4 increased by 1 and lnTSH decreased by 0.03, 3.52, respectively. In case of a stressful event on OQ, lnTSH increased by 1.55. In the high-risk group, lnTSH increased by 0.79, compared with the low group (p<0.05). TSH had a significant relationship with stress, together with T3, T4, and the extent of thyroidectomy. As such, it has the potential to be used as a stress marker, though it showed a low correlation with other stress questionnaires. To address this limitation, questionnaires on various social environments and research on copy strategies are necessary for future studies.

Keywords: stress, surgery, thyroid stimulating hormone, thyroidectomy

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Authors: So Youn Park, Yi Sle Lee, Ki Whan Hong, Chi Dae Kim

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The role of metabolism in the pathogenesis of osteoarthritis is an emerging field. Metabolic alterations may be a role in osteoarthritis (OA) pathogenesis, and these changes influence joint destruction via several cytokine. Especially, in OA patients, levels of IL-1β are elevated in the synovial fluid, synovial membrane, subchondral bone, and cartilage. The IL-1β is activated by NLRP3 inflammasomes, and NLRP3 inflammasomes are cytosolic complexes that drive the production of other inflammatory cytokines, including IL-1β. In this study, we examined that SIRT1 suppresses IL-1β through inhibiting NLRP3 inflammasomes and SIRT1 ameliorates osteoarthritis. OA fibroblasts were isolated from synovium of OA patients. IL-1β and NLRP3 were detected in synovium of OA patients by immunohistochemistry. Lipopolysaccharides (LPS) stimulated the expression of active IL-1β mRNA in OA fibroblasts and combination of LPS, and adenosine triphosphate increased more the expression of active IL-1β in OA fibroblasts. The level of IL-1β was measured by western blot and ELISA assay. NLRP3 inflammasomes complex were measured by western blot. SIRT1 did not inhibit expression of NLRP3 inflammasome. So caspase-1, apoptotic speck-like protein containing a caspase recruitment domain (ASC) and NLRP3 protein were expressed in OA fibroblasts. But SIRT1 suppressed activation of IL-1β by inhibiting activity of caspase-1 via NLRP3 inflammasome in OA fibroblasts under LPS plus ATP stimulation. These results suggest that SIRT1 is a modulator of NLRP3 inflammasomes in OA fibroblasts and ameliorate IL-1β, so expression of SIRT1 in OA fibroblast may be a potential strategy for OA inflammation treatment.

Keywords: osteoarthritis, inflammasome, SIRT1, IL-1beta

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Authors: Lamees A. Ben Saad, Kah Hwi Kim, Chin Chew Quah, Mustafa Shahimi

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Background: Punica granatum (pomegranate) was used as a traditional medicine in different parts of the world. It has been used in the treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of the ethyl acetate pomegranate fraction (EtOAc) by determination of its inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX2) release from RAW264.7cells. Methods: The inhibitory effect of EtOAc was evaluated on (LPS) induced NO production, PGE2, and IL-6 quantified by immunoassay kit and prostaglandin E2 competitive ELISA kit. COX2 production is an in vitro indication of possible anti-inflammatory activity and was estimated by Western blotting. Results: EtOAc potentially inhibited LPS-induced nitric oxide, prostaglandin, and IL-6 production. With these findings, it was evident that the EtOAc could reduce the LPS-induced cyclooxygenase-2 (COX-2) at the protein level in a dose-dependent manner as determined by Western blotting. Conclusion: The results emphasize potential therapeutic applications of Punica granatum in the treatment of inflammation.

Keywords: inflammation, Punica granatum, cytotoxicity, cytokines

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Authors: Corina Muscurel, Irina Stoian, Laura Gaman, Valeriu Atanasiu

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Chronic inflammation predisposes cells to neoplastic transformation and is associated with angiogenesis. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) give rise to anti-inflammatory metabolites and decrease some inflammatory cytokines. The aim of the study was to analyze the effect of n-3 PUFAs intake on patients with tumors in early-stage (without regional or distant metastasis). There were two groups of patients: one group with colon tumors and one group with lung tumors. All patients took for 60 days daily supplements from fish-oil containing 600 mg eicosapentaenoic acid and 400 mg docosahexaenoic acid. The plasma markers were evaluated before and after PUFAs intake: ceruloplasmin (using p-phenylenediamine oxidase method), plasma total thiol groups (using dithiobis-nitrobenzoic acid method) and CEA (carcinoembryonic antigen using electrochemiluminescent immunoassay). The results reflect ceruloplasmin decrease (p < 0.05), plasma total thiol groups increase (not statistically significant) and CEA decrease (p < 0.05) after n-3 PUFAs intake. Conclusions: n-3 PUFAs intake is favorable in premalignant lesions or in early tumor stage and dietary fish-oil has anti-inflammatory effects and can contribute to reduce cancer progression.

Keywords: cancer, fish-oil, inflammation, n-3 polyunsaturated fatty acids

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Authors: Francesca La Rosa , Marina Saresella, Mario Clerici, Michael Heneka

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Neuroinflammation plays a key role in the modulation of the pathogenesis of neurodegenerative disorder such as Alzheimer's Disease (AD). Microglia, the main immune effector of the brain, are able to migrate to sites of Amyloid-beta (Aβ) deposition to eliminate Aβ phagocytosis upon activation by multiple receptors: Toll like receptors and scavenger receptors. The issue of whether microglia are able to eliminate pathological lesions such as neurofibrillary tangles or senile plaques from AD brain still remains the matter of controversy. Recent data suggest that the Nod Like Receptor 3 (NLRP3), multiprotein inflammasome complexes, plays a role in AD, as its activation in the microglia by Aβ triggers. IL-1β is produced as a biologically inactive pro-form and requires caspase-1 for activation and secretion. Caspase-1 activity is controlled by inflammasomes. We investigate about the importance of inflammasomes complex in the Aβ phagocytosis and its degradation. The preliminary results of phagocytosis assay and immunofluorescent experiment on primary Microglia cells to lipopolysaccharide (LPS) an Aβ exposure show that a previous treatment with LPS reduce Aβ phagocytosis. Different results were obtained in Primary Microglia wild type, NLRP3 and ASC Knockout suggesting a real inflammasomes involvement in Alzheimer's pathology. Inflammasomes inactivation reduces the production of inflammatory cytokines prolonging the protective activity of microglia and Aβ clearance, featuring a typical microglia phenotype of the early stage of AD disease.

Keywords: Alzheimer disease, innate immunity, neuroinflammation, NLRP3

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Authors: Mohammaad Afzal Khan, Ghazi Abdulmalik Ashoor , Fatimah Alanazi, Talal Shamma, Abdullah Altuhami, Hala Abdalrahman Ahmed, Abdullah Mohammed Assiri, Dieter Clemens Broering

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Microvascular injuries during inflammation are key causes of transplant malfunctioning and permanent failure, which play a major role in the development of chronic rejection of the transplanted organ. Inflammation-induced microvascular loss is a promising area to investigate the decisive roles of regulatory and effector responses. The present study was designed to investigate the impact of IL-10 on immunotolerance, in particular, the microenvironment of the allograft during rejection. Here, we investigated the effects of IL-10 blockade/ reconstitution and serially monitored regulatory T cells (Tregs), graft microvasculature, and airway epithelium in rejecting airway transplants. We demonstrated that the blocking/reconstitution of IL-10 significantly modulates CD4+FOXP3+ Tregs, microvasculature, and airway epithelium during rejection. Our findings further highlighted that blockade of IL-10 upregulated proinflammatory cytokines, IL-2, IL-1β, IFN-γ, IL-15, and IL-23, but suppressed IL-5 secretion during rejection; however, reconstitution of IL-10 significantly upregulated CD4+FOXP3+ Tregs, tissue oxygenation/blood flow and airway repair. Collectively, these findings demonstrate a potential reparative modulation of IL-10 during microvascular and epithelial repair, which could provide a vital therapeutic window to rejecting transplants in clinical practice.

Keywords: interleukin -10, regulatory T cells, allograft rejection, immunotolerance

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Authors: Emma Plante, Charles Ekwunwa, Diego Illanes

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Introduction: Serum Sickness-Like Reaction (SSLR) is an inflammatory immune response characterized by a rash, polyarthralgias, and fever. SSLR usually occurs in response to a new medication (most commonly antibiotics, anticonvulsants, or antiinflammatory agents) and is believed to involve the formation of drug-specific immune complexes. Here we present a case of a 16-year-old female patient who developed an SSLR in response to the D-mannose-containing over-the-counter supplement, Uqora, used to promote bladder health. Methodology: The methodology for this study included a thorough literature search for other cases of SSLR associated with D-Mannose containing products. Data collection was performed through a review of the patient’s medical record, including history, physical examination, relevant laboratory results, and treatment plan. Findings: A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. Her CBC, basic metabolic panel, liver function panel, lyme titers, and urinalysis were all within normal limits. The patient was referred to an allergist, who diagnosed her with SSLR. All medications were discontinued, and she was treated with a 7-day course of prednisone and cetirizine. Her symptoms resolved, and her medications were slowly resumed sequentially over several months. However, UQora triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free. Conclusion: This case report describes the first documented case of SSLR caused by UQora (active ingredient D-mannose). D-Mannose is a monosaccharide found in many plants and fruits, and it is commonly used to prevent urinary tract infections. While the clinical features and timeline, in this case, were typical of SSLR, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of SSLR and the importance of prompt identification and management to enhance patient safety. It is possible D-mannose was not the trigger, and further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.

Keywords: serum sickness-like reaction, d-mannose, hypersensitivity reaction, urticaria

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Authors: Ping-Lun Jiang, Hung-Jun Lin, Shen-Fu Lin, Mei-Yin Chien, Ting-Wei Li, Chun-Han Lin, Der-Zen Liu

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Mucosal vaccine induces both mucosal (secretory IgA) and systemic immune responses and it is considered an ideal vaccination strategy for prevention of infectious diseases. One important point to be considered in mucosal vaccination is effective antigen delivery system which can manage effective delivery of antigen to antigen-presenting cells (APCs) of mucosal. In the present study, cationic gelatin nanoparticles were prepared as ideal carriers for more efficient antigen delivery. The average diameter of cationic gelatin nanoparticle was approximate 190 nm, and the zeta potential was about +45 mV, then ovalbumin (OVA) was physically absorbed onto cationic gelatin nanoparticle. The OVA absorption rate was near 95% the zeta potential was about +20 mV. We show that cationic gelatin nanoparticle effectively facilitated antigen uptake by mice bone marrow-derived dendritic cells (mBMDCs) and RAW264.7 cells and induced higher levels of pro-inflammatory cytokines. C57BL/6 mice twice immunized intranasally with OVA-absorbed cationic gelatin nanoparticle induced high levels of OVA-specific IgG in the serum and IgA in their in the nasal and lung wash fluid. These results indicate that nasal administration of cationic gelatin nanoparticles induced both mucosal and systemic immune responses and cationic gelatin nanoparticles might be a potential antigen delivery carrier for further clinical applications.

Keywords: antigen delivery, antigen-presenting cells, gelatin nanoparticle, mucosal vaccine

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Authors: M. Toygar, I. Aydin, M. Agilli, F. N. Aydin, M. Oztosun, H. Gul, E. Macit, Y. Karslioglu, T. Topal, B. Uysal, M. Honca

Abstract:

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon g and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1 (TGF-1) levels were significantly higher than the sham group (in all, p< 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p 1/4 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1 levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Keywords: paraquat, inflammation, oxidative stress, neopterin, lung toxicity

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Authors: Abbassi Daloii Asieh, Yazdani Hoda

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Background and Objective: evidence supports systemic inflammation in obesity and insulin resistance. Apelin that is secreted by adipose tissue plays an important role in the inflammation process and appear act as an anti-inflammatory cytokines. The aim of this study was the effect of eight weeks aerobic training and nitro-L-arginine-methyl ester (L-NAME) on plasma apelin in male’s rats. Materials and Methods: For this purpose, 24 male Wistar rats aged 20 months were randomly assigned into four groups: Control, training, training and L-NAME and L-NAME. Training intervention was eight weeks aerobic exercise (5 time/weekly) at 75-80 (%) of maximal oxygen consumption. All rats were killed 72 hours after lasted exercise session; blood samples collected and plasma were stored. Data was analyzed by one way ANOVA and Tucky Test. A p value less than 0.05 was considered statistically signigcant. Results: The results showed that after eight weeks of endurance training exercise Apelin plasma compared to the control group did not change significantly. Also, the results showed that there was significant difference in plasma Apelin between groups(P > 0/05). Also, the results showed no significant difference between the insulin levels and glucose of four groups (P > 0/05). Conclusion: It seems that aerobic exercise plasma Apelin levels in male rats is not affected. On the other hand, nitric oxide inhibitors can reduce levels of plasma Apelin.

Keywords: aerobic training, L-NAME, plasma Apelin, male’s rats

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Authors: Chao Hsing Yeh, Wei Chun Lin

Abstract:

Background: Current management of aromatase inhibitor-induced arthralgia (AIA) in postmenopausal breast cancer survivors (PBCS) has limited effect. Method: In this prospective randomized clinical trial (RCT), a 4-week APA treatment was used to manage AIA. Twenty PBCS participated. After baseline data was collected, participants were waited for a month before they receive APA at a convenient time once a week for 4 weeks. Blood samples from participants in both groups were collected at baseline and after 4 weeks of treatment. The primary outcomes included: pain intensity, pain interference, stiffness, and physical function. Results: After the 4-week APA treatment, the pro-inflammatory cytokines and chemokines display a trend of mean percentage reduction (i.e., -22% in IL-1α, -4% in IL-1β, -1% in IL-2, -3% in IL-6, -19% in IL-12, -9% in Eotaxin, and -2% in MCP-1). The anti-inflammatory cytokine IL-10 and IL-13 (i.e., 5% in IL-10 and 29% in IL-13) increased from pre- to post-APA treatment. Significant positive correlation of percentage mean change was observed between symptom severity and eotaxin (ρ = 0.56; p < 0.01) & MCP-1 (ρ = 0.65; p < 0.01). Interference and chemokines (eotaxin & MIP-1) also shows positive correlation (ρ = 0.48; p < 0.01 & ρ = 0.39; p < 0.05). Another positive correlation was found between worst pain and chemokines (eotaxin, ρ = 0.48; p < 0.01 & MIP-1, ρ = 0.39; p < 0.05). Additionally, interference also shows positive correlation among IL-1α (ρ = 0.36; p < 0.05) and IL-β (ρ = 0.33; p < 0.05). Conclusion: These findings suggest that APA intervention may inhibit inflammation of AIA patients and chemokine could be one of the key factors of AIA symptom improvement.

Keywords: acupressure, cytokine, pain management, breast cancer survivors

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Authors: Chakrit Thapphan, Suteeraporn Chaowattanapanit, Sorutsiri Chareonsudjai, Wisitsak Phoksawat, Supranee Phantanawiboon, Kiatichai Faksri, Steve W. Edwards, Kanin Salao

Abstract:

Background: Psoriasis is a chronic inflammatory disease of the skin that is mediated by crosstalk between keratinocytes and immune cells, especially CD4+ T helper (Th) cells. To date, psoriasis is established as a T helper 17 (Th17) cell-mediated inflammatory process driven by the over-expression of Th17. However, the role of other CD4+T helper cells is rather controversial. Objective: Our study, thereby, aimed to characterize and analyze T cell subsets in the circulating blood of psoriasis patients and compare them to healthy controls. Methods: Peripheral blood mononuclear cells were isolated from the participants and stained with fluorescent dye-conjugated monoclonal antibodies specific for intracellular cytokines, including interferon-gamma (IFN- γ), interleukin (IL-4), IL-17 and forkhead box P3 (FOXP3), that can be used to define T helper 1 (Th1) cells, T helper 2 (Th2), T helper 17 (Th17) and regulatory T cells (Treg) respectively. Results: We found that the numbers of Th2 (59.6% ± 17.0) and Th17 (4.0% ± 2.0) cells in the circulating blood of psoriasis patients were significantly higher than those of the healthy controls (p= 0.0007 and 0.0013 respectively). In contrast, the numbers of Th1 and Treg cells were not significantly different between psoriasis patients and healthy controls (p= 0.0593 and 0.8518, respectively). Additionally, when adjusting these numbers of Th cells to Treg, we observed a similar trend that the ratio of Th2/Treg and Th17/Treg also elevated (p = 0.0007 and 0.0047, respectively). Conclusion: Taken together, our results suggest an imbalanced T exhibit toward the Th2 and Th17 skewed-immune responses in psoriasis patients.

Keywords: psoriasis, Th cell subsets, Th2 cells, Th17 cells, Treg cells

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Authors: Xiaoyan Jiang, Huizhu Wang, Lili Gui, Dandan Shen, Xiao Wei, Xi Yu, Hailiang Liu, Min Hong

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Objective: Applicate FITC to establish Th2-type allergic contact dermatitis model, and study the effect and mechanism of Cimifugin on Th2-type allergic contact dermatitis. Methods: The Balb/c mice were sensitized with painting 80 ul of 1.5% FITC onto the shaved abdomen skin at DAY1 and DAY2. The animals were challenged on their right ears with 20 ul of 0.6% FITC, and the left ears were painted with solvent alone at day 6, mice were administered cimifugin for 7 days. 24h later, ear swelling was noted, and the infiltration of eosinophils was investigated by hematoxylin and eosin (H&E) staining. while part of the ear tissue homogenates prepared for detecting interleukin-4 levels by ELISA .Mice were administered cimifugin In the initial stage of the above model for 5 days(-1DAY—DAY3), ear tissue were homogenized to detect IL-33 levels by ELISA. Results: Cimifugin 25mg/kg, 50mg/kg inhibited mouse ear swelling, ear histopathology showed that mice given Cimifugin has significantly reduced levels of local tissue fluid exudation, congestion, infiltration of lymphocytes, and other inflammatory conditions compared with the model group. At the same time, it has significantly reduce of Th2 cytokines IL-4 in the mouse ear tissue homogenate. Data of the initial stage shows that 12.5mg/kg, 50mg/kg Cimifugin significantly inhibited IL-33 levels. Conclusion: Cimifugin inhibit FITC-induced Th2-type allergic contact dermatitis, and its mechanism may be related to inhibition of IL-33.

Keywords: cimifugin, allergic contact dermatitis, Th1/Th2, IL-33

Procedia PDF Downloads 446