Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 32759
Changes of in vitro Cytokine Production induced by δ-Lactams

Authors: Y. Baba hamed, A. Medjdoub, H. Merzouk, M. Narce

Abstract:

The aim of this work was to study the in vitro effects of δ-lactam 1 and its 4-chlorophenyl derivative 2, on the proliferative responses of human lymphocytes and Th1 and Th2 cytokine secretion. The possible protective role of vitamin E on intracellular stress oxidative induced by these compounds was also investigated. Peripheral blood lymphocytes were isolated using differential centrifugation on a density gradient of Histopaque. They were cultured with mitogen concanavalin A, vitamin E (10 μM) and with different concentrations of the compounds 1 and 2 (0.1 to 10 μM). Proliferation (MTT assay), IL-2, INFγ and IL-4 (Elisa kits), intracellular superoxide anion were determined. 1 and 2 were immunostimulant and increased cytokine secretion with a shift away from Th1 response to Th2. These properties were however accompanied by an increase in intracellular oxidative stress. The presence of vitamin E exhibited protective effects by reducing δ- lactam-induced superoxide anion generation in lymphocytes.

Keywords: Cytokines, δ-Lactams, In vitro Lymphocyte Proliferation, Superoxide Anion

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1331575

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 3815

References:


[1] B. Zygmunt and M. Veldhoen, "T helper cell differentiation more than just cytokines", Adv. Immunol., 109:159-196, 2011.
[2] T.T. Mossman and S. Sad, "The expanding universe of T-cell subsets: Th1, Th2 and more", Immunol. Today, 17:138-146, 1996.
[3] D.A. Mata-Espinosa and R. Hernández-Pando, "Gamma interferon: basics aspects, clinic significance and terapeutic uses", Rev. Invest. Clin., 60:421-431, 2008.
[4] D. Amsen, C.G. Spilianakis and R.A. Flavell, "How are T(H)1 and T(H)2 effector cells made?", Curr. Opin. Immunol., 21:153-160, 2009.
[5] J.C.S. Bergh, T.H. Tötterman, B.C. Termander, K.A. Strandg├Ñrden, P.O.G. Gunnarsson and B.I. Nilsson, "The first clinical pilot study of roquinimex (Linomide) in cancer patients with special focus on immunological effects", Cancer Invest., 15:204-211, 1997.
[6] J.B. Calixto, M.M. Campos, M.F. Otuki and A.R.S. Santos ARS, "Anti-inflammatory compounds of plants origin, modulation of proinflammatory cytokines, chemokines and adhesion molecules" , Planta Med., 70:93-103, 2004.
[7] G. Hedlund, H. Link, J. Zhu and B.G. Xiao, "Effects of Linomide on immune cells and cytokines inhibit autoimmune pathologies of the central and peripheral nervous system", Int. Immunopharmacol., 1:1123-1130, 2001.
[8] A.M. Thompson, G.W. Rewcastle, S.L. Boushelle, B.G. Hartl, A.J. Kraker, G.H. Lu, B.L. Batley, R.L. Panek, H.D. Showalter and W.A. Denny, "Synthesis and structure-activity relationships of 7-substituted 3-(2, 6-dichlorophenyl)-1,6-naphthyridin-2(1H)-ones as selective inhibitors of pp60(c-src)", J. Med. Chem., 43:3134-3147, 2000.
[9] P. Traxler P, "Tyrosine kinases as targets in cancer therapy - successes and failures", Expert Opin. Ther. Targets, 7:215-234, 2003.
[10] Y. Baba Hamed, A. Medjdoub, B. Mostefa Kara, H. Merzouk, D. Villemin and M. Narce, "5,6-Dihydro-2H-pyranones and 5,6-dihydro- 2H-pyridones and their derivatives modulate in vitro human T lymphocyte function", Mol. Cell. Biochem., 360:23-33, 2012.
[11] D. Jansone, S. Belyakov, M. Fleisher, L. Leite and E. Lukevics, "Molecular and crystal structure of 4,6,6-trimethyl- 2-oxo-5,6-dihydro- 2h-pyran- 3-carbonitrile and 4,6,6-trimethyl- 2-oxo-1,2,5,6 tetrahydropyridine- 3-carbonitrile", Chem. Heterocycl. Comp., 43:1374-1378, 2007.
[12] E. Lukevic, D. Jansone, E. Leite, J. Popelis, G. Andreeva, L. Shestakova, I. Domracheva, V. Bridane and I. Kanepe, "Synthesis and cytotoxicity of phenyl- vinyl derivatives of 4,6,6-trimethyl-2-oxo- 1,2,5,6-tetrahydropyridine-3-carbonitrile", Chem. Heterocycl. Comp., 45: 1226-1234, 2009.
[13] T. Mossman, "Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays", J. Immunol. Methods, 65: 55-63, 1983.
[14] Ramanathan R, Das NP, Tan CH (1994) Effects of -y-linolenic acid, flavonoids, and vitamins on cytotoxicity and lipid peroxidation. Free Rad Biol Med 16: 43-48
[15] J. Roth and G.E.P. De Souza, "Fever induction pathways: evidence from responses to systemic or local cytokine formation", Braz. J. Med. Biol. Res., 34:301-314, 2001.
[16] H.M. Kim, D.K. Ryu, Y. Choi, B.W. Park, K. Lee, S.B. Han, C. Lee, M.R. Kang, J.S. Kang, S.K. Boovanahalli, S. Park, J.W. Han, T. Chun, H.Y. Lee, K. Nam, E.H. Choi and G. Han, "Structure -activity relationship studies of a series of novel ╬│-Lactam- based histone deacetylase inhibitors", J. Med. Chem., 50:2737-2741, 2007.
[17] J.J. Mond, A. Balapure, N. Feuerstein, J.H. June, M. Brunswick, M.L. Lindsberg and K. Witherspoon, "Protein kinase C activation in B cells by indolactam inhibits anti-Ig- mediated phosphatidylinositol bisphosphate hydrolysis but not B cell proliferation", J. Immunology, 144:451-455, 1990.
[18] M.P. Zanni, S.V. Greyerz, B. Schnyder, C.K. Brander, K. Frutig, Y. Hari, S. Valitutti and W.J. Pichler, "HLA-restricted, Processing- and Metabolism-independent Pathway of Drug Recognition by Human ╬▒βT Lymphocytes", J. Clin. Invest., 102:1591-1598, 1998.
[19] D.A. Hildeman, T. Mitchell and T.K. Teague, "Reactive oxygen species regulate activation-induced T cell apoptosis", Immunity, 10:735-744, 1999.
[20] A. Fico, F. Paglialunga, L. Cigliano, P. Abrescia, P. Verde, G. Martini, I. Iaccarino and S. Filosa, "Glucose-6-phosphate dehydrogenase plays a crucial role in protection from redox-stressinduced apoptosis", Cell Death Different., 11:823-831, 2004.
[20] B. Frossi, M. De Carli, M. Piemonte and C. Pucillo, "Oxidative microenvironment exerts an opposite regulatory effect on cytokine production by Th1 and Th2 cells", Mol. Immunology, 45:58-64, 2008.
[22] C. Y. Lee and J.M. Wan , "Vitamin E supplementation improves cellmediated immunity and oxidative stress of Asian men and women" , J. Nutr., 130: 2932-2937, 2000.
[23] X.H. Wang, X.Q. Zhou, J.P. Xu, Y. Wang and J. Lu, "The effects of vitamin E on NK cell activity and lymphocyte proliferation in treated mice by 2,3,7,8-tetrachlorodibenzo-p-dioxin", Immunopharmacol. Immunotoxicol., 1-7, 2009.
[24] L. Alpsoy, A. Yildirim and G. Agar, "The antioxidant effects of vitamin A, C, and E on aflatoxin B1-induced oxidative stress in human lymphocytes", Toxicol. Ind. Health, 25: 121-127, 2009.