The Effect of Physical Exercise to Level of Nuclear Factor Kappa B on Serum, Macrophages and Myocytes

Authors: Eryati Darwin, Eka Fithra Elfi, Indria Hafizah

Abstract:

Background: Physical exercise induces a pattern of hormonal and immunological responses that prevent endothelial dysfunction by maintaining the availability of nitric oxide (NO). Regular and moderate exercise stimulates NO release, that can be considered as protective factor of cardiovascular diseases, while strenuous exercise induces increased levels in a number of pro-inflammatory and anti-inflammatory cytokines. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) triggers endothelial activation which results in an increased vascular permeability. Nuclear gene factor kappa B (NF-κB) activates biological effect of TNF-α. Aim of Study: To determine the effect of physical exercise on the endothelial and skeletal muscle, we measured the level of NF-κB on rats’ serum, macrophages, and myocytes after strenuous physical exercise. Methods: 30 male Rattus norvegicus in the age of eight weeks were randomly divided into five groups (each containing six), and there were treated groups (T) and control group (C). The treated groups obtain strenuous physical exercise by ran on treadmill at 32 m/minutes for 1 hour or until exhaustion. Blood samples, myocytes of gastrocnemius muscle, and intraperitoneal macrophages were collected sequentially. There were investigated immediately, 2 hours, 6 hours, and 24 hours (T1, T2, T3, and T4) after sacrifice. The levels of NF-κB were measured by ELISA methods. Results: From our study, we found that the levels of NF-κB on myocytes in treated group from which its specimen was taken immediately (T1), 2 hours after treadmill (T2), and 6 hours after treadmill (T3) were significantly higher than control group (p<0.05), while the group from which its specimen was taken 24 hours after treadmill, was no significantly different (p>0.05). Also on macrophages, NF-κB in treated groups T1, T2, and T3 was significantly higher than control group (p<0.05), but there was no difference between T4 and control group (p>0.05). The level of serum NF-κB was not significantly different between treatment group as well as compared to control group (p>0.05). Serum NF-κB was significantly higher than the level on macrophages and myocytes (p<0.05). Conclusion: This study demonstrated that strenuous physical exercise stimulates the activation of NF-κB that plays a role in vascular inflammation and muscular damage, and may be recovered after resting period.

Keywords: Endothelial function, inflammation, NF-κB, physical exercise.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1128915

References:

[1] CJ Caspersen, KE Powell and GM Christenson. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep. 1985;100:126–131
[2] KM Diaz and D Shimbo. Physical Activity and the Prevention of Hypertension. Curr Hypertens Rep. 2013; 15.6: 659-668.
[3] C Handschin AND BM Spiegelman. The role of exercise and PGC1α in inflammation and chronic disease. Nature 2008; 454:463-469.
[4] WHO, 2008 World Health Organization. Review of Best Practice in Interventions to Promote Physical Activity in Developing Countries, 2008
[5] T Ibfelt, EW Petersen, H Bruunsgaard, M Sandmand, and BK Pedersen. Exercise-induced change in type 1 cytokine-producing CD8+ T cells is related to a decrease in memory T cells. J Appl Physiol,2002; 93: 645–648
[6] GI Lancaster, Q Khan, PT Drysdale, F Wallace, AE Jeukendrup, MT Drayson,et al. Effect of prolonged exercise and carbohydrate ingestion on type 1 and type 2 T lymphocyte distribution and intracellular cytokine production in humans. J Appl Physiol, 2005; 98. 2: 565-571
[7] M Gleeson. Immune function in sport and exercise. J Appl Physiol, 2007; 103.2: 693-9
[8] R Terra, SAG da Silva, VS Pinto, K, Patrícia and ML Dutra. Effect of exercise on the immune system: response, adaptation and cell signaling. Rev Bras Med Esporte,2012;18.3:208-221
[9] Flyn M, McFarlin BK, Markofski MA. The anti-inflammatory actions of exercise training. Am J Lifestyle Med 2007;1:220-235
[10] BK Pedersen and MA Febbraio. Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6. Physiol Rev 2008;88:1379-1406
[11] D Nieman. Exercise effects on systemic immunity. Immunology and Cell Biology,2000; 78; 496–501
[12] GA Gannon, S Rhind, PN Shek and RJ Shephard. Naïve and memory T cell subsets are differentially mobilized during physical stress. Int J Sports Med,2002; 23: 223–229,
[13] A Moretta, E Marcenaro, S Parolini, G Ferlazzo and L Moretta. NK cells at the interface between innate and adaptive immunity. Cell Death Differ 2008;15:226-233
[14] NP Walsh, M Gleeson and RJ Shephard. Position statement. Part one: immune function and exercise. Exerc Immunol Rev. 2011;17:6-63
[15] K Kruger, A Lechtermann, M Fobker, K Volker and FC Mooren. Exercise-induced redistribution of T lymphocytes is regulated by adrenergic mechanisms. Brain Behave Immun 2008;22:324-338.
[16] DJ Green, A Maiorana, G O’Driscol, R Taylor. Effect of exercise training on endothelium-derived nitric oxide function in humans. J Physiol, 2004; 561: 1–25.
[17] A Nunes-Silva. Exercise-Induced Inflammatory Response: To Use or Not use Anti-Inflammatory Medication. J Sports Med Doping Stud, 2014; 4:142-149
[18] LL Ji. Redox signaling in skeletal muscle: role of aging and exercise. Advances in Physiology Education, 2015;39. 4: 352-359
[19] Cleto LS, Oleto AF, Sousa LP, Barreto TO, Cruz JS, Penaforte CL, et al. Plasma cytokine response, lipid peroxidation and NF-κB activation in skeletal muscle following maximum progressive swimming. Braz J Med Biol Res, 2011; 44.6 : 546-552
[20] Kramer HF and Goodyear LJ. Exercise, MAPK, and NF-κB signaling in skeletal muscle. J Appl Physiol,2007; 103: 388–395
[21] Y Wang, U Wisloff and J Kemi. Animal Models in the Study of Exercise-Induced Cardiac Hypertrophy. Physiol. Res, 2010; 59: 633-644
[22] W Frank. F Booth, V Manu. Chakravarthy, E Scott, K Gordon et al., Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy. Journal of Applied Physiology, 2002; 93. 1: 3-30
[23] SK Powers, and MJ Jackson. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev 2008; 88: 1243–1276
[24] AM Sanchez, RB Candau, H Bernardi. FoxO transcription factors: their roles in the maintenance of skeletal muscle homeostasis. Cell Mol Life Sci, 2014;71: 1657–1671
[25] K Sakamoto, and LJ Goodyear. Intracellular signaling in contracting skeletal muscle. J Appl Physiol,2002; 93: 369–383
[26] LL Ji, MC Gomez-Cabrera, N Steinhafel, and J Vina. Acute exercise activates nuclear Factor (NF) κB signaling pathway in rat skeletal muscle. FASEB J,2004; 18: 1499–1506
[27] MC Gomez-Cabrera, C Borras, FV Pallardó, JSastre, LL Ji, and J Viñ. Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats. J Physiol,2005; 567: 113–120
[28] MA Febbraio, BK Pedersen. Contraction-induced myokine production and release: is skeletal muscle an endocrine organ? Exerc Sport Sci Rev 2005;33:114-119.
[29] A Pinto, D Di Raimondo, A Tuttolomondo, C Buttà, G Milio, and GLicata. Effects of physical exercise on inflammatory markers of atherosclerosis. Curr Pharm, 2012;18.28:4326-4349.
[30] B Hoesel and J Schmid.The complexity of NF-κB signaling in inflammation and cancer. Molecular Cancer.2013;12:86-93
[31] C Keller, P Keller, M Giralt, J Hidalgo, BK Pedersen. Exercise normalises overexpression of TNF-α in knockout mice. Biochem. Biophys Res Commun 2004;321:179-182.
[32] TM Tinken, HJ Dick, Thijssen, N Hopkins, and EA Dawson. Shear Stress Mediates Endothelial Adaptations to Exercise Training in Humans. Hypertension. 2010;55:312-318
[33] B D'Autréaux, MB Toledano. ROS as signaling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol,2007; 8: 813–824
[34] Y Collins, ET Chouchani, AM James, KE Menger, HM Cochemé, MP Murphy. Mitochondrial redox signaling at a glance. J Cell Sci,2012; 125: 801–806
[35] C Berneckr , J Scherr, S Schinner , S Braun , WA Scherbaum , M Halle . Evidence for an exercise induced increase of TNF-α and IL-6 in marathon runners. Scand J Med Sci Sports, 2013;23.2:207-217.