اثر شدت های مختلف فعالیت حاد و مزمن هوازی بر مسیر پیام رسان اینفالامازومNLRP3 ، TLR4 و سطوح سایتوکاین های التهابی در مردان جوان

نوع مقاله: مقاله پژوهشی

نویسندگان

1 دکتری فیزیولوژی ورزشی، گروه فیزیولوژی ورزشی، دانشگاه گیلان، رشت، ایران.

2 استاد فیزیولوژی ورزشی، گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه گیلان، رشت، ایران.

3 استاد بیوشیمی بالینی، انستیتو ارتوپدیک گالاتزی، میلان، ایتالیا.

10.22077/jpsbs.2019.1982.1454

چکیده

زمینه و هدف: نتایج مطالعات نشان می دهد که شدت و حجم فعالیت ورزشی هوازی بر سیستم ایمنی پاسخ های متفاوتی دارد. هدف تحقیق حاضر، بررسی اثر حاد و مزمن تمرینات هوازی با شدت متوسط و بالا بر مسیر پیام رسان اینفالامازوم NLRP3، گیرنده شبه گذرگاهی 4 (TLR4) و سطوح سایتوکاین های التهابی در مردان جوان بود. روش تحقیق: تعداد 60 نفر به طور تصادفی (بر اساس پیشینه تحقیق) به دو گروه تمرین ( هر گروه 20 نفر) و در گروه کنترل (20 نفر) تقسیم شدند. پروتکل های تمرینی برای گروه تمرین متوسط از شدت 50 درصد ضربان قلب بیشینه شروع و با افزایش تدریجی با شدت 70 درصد ضربان قلب بیشینه به اتمام رسید. برای گروه بـا شـدت بـالا نیز تمرین با شدت 70 درصد شروع و با شدت 90 درصد ضربان قلب بیشینه به اتمام رسید. با استفاده از روش Real time-Pcr  بیان ژن های NLRP3 وTLR4  و با روش الایزا سطوح سرمیIL-1β  و  IL-18 اندازه گیری شد. جهت تجزیه و تحلیل داده‌ها از آزمون تحلیل واریانس (ANOVA) با اندازه گیری مکرر و آزمون تعقیبی LSD استفاده شد و سطح معنی داری آزمون ها 0/05>p در نظر گرفته شد. یافتـه ها: نتایـج نشان داد که تمرین حاد تک جلسه ای هـوازی با شدت متوسط تاثیـر معنی داری بر بیان ژن های TLR4 (p=0/80) و NLRP3 (p=0/20) و سطوح سرمی IL-1β (p=0/15) و IL-18 (p=0/25) ندارد؛ در حالی که تمرین حاد با شدت بالا با افزایـش معنـی دار سطوح  IL-1β و IL-18 و بیان ژن های NLRP3 وTLR4  همـراه است (0/01<p). همچنین تمرینات مزمن هوازی با شدت متوسط باعث کاهش معنی دار بیان ژن های NLRP3 وTLR4  و سطوح IL-1β  و  IL-18 شد (0/001<p) و بـر عکس، تمرین مزمن با شدت بالا، افزایش معنی دار  در بیان ژن های TLR4 و  NLRP3 و سطوح IL-1β و  IL-18  را بـه همـراه داشـت (0/0001<p). نتیجه گیری: احتمالاً فعالیت مزمن هوازی با شدت متوسط می تواند در تنظیم کاهشی مسیر اینفالامازوم و التهاب موثر باشد، در صورتی که فعالیت حاد هوازی با شدت های مختلف، تاثیری بر کاهش مسیرهای التهابی ندارد.

کلیدواژه‌ها


عنوان مقاله [English]

The effect of different intensities of acute and chronic aerobic activity on the signaling pathway of the inflammasome NLRP3 complex and TLR4 and some inflammatory cytokines in young men

نویسندگان [English]

  • Iman khakroo Abkenar 1
  • Farhad Rahmani-nia 2
  • Giovanni Lombardi 3
1 PhD of Exercise Physiology, Department of Exercise Physiology, University of Guilan, Rasht, Iran.
2 Full Professor, Department of Exercise Physiology, Faculty of Sport Sciences, University of Guilan, Rasht, Iran.
3 Full Professor, IRCCS Istituto Ortopedico Galeazzi, Laboratory of Experimental Biochemistry and Molecular Biology, via Riccardo Galeazzi, Milan, Italy.
چکیده [English]

Background and Aim: The results of the studies showed that the intensity and volume of aerobic exercise activities can make different responses to the immune system. The purpose of this study was to investigate the acute and chronic effects of moderate and high intensity aerobic exercises on the signaling pathway of the inflammatory NLRP3 complex or TLR4 and some inflammatory cytokines in young men. Materials and Methods: A randomized sampling method was used in which 60 subjects were selected based on their research. They were randomly divided into two groups (40 subjects) with a mean age of 24.4 ± 0.4 years and a BMI of 23.3 ± 3.5 kg/m2 and in the control group (20 persons) with a mean age of 22.8 ± 0.55 years and BMI of 23.0 ± 4.91 kg/m2. The training protocol for the moderate group performed up to 50 - 70 and for the high group up to 70 – 90 percent of maximum heart rate respectively. Using real time-PCR method, the expression of NLRP3, TLR4 genes and using the Elisa method IL-1β and IL-18 were measured. Also repeated measure ANOVA and the LSD post hoc- test were used to analyzing data at the significant level of p < 0.05. Results: The results showed that acute aerobic exercise with moderate intensity had no significant effect on the expression of NLRP3 (p=0.20), TLR4 (p=0.80) genes and serum levels of IL-1β (p=0.15) and IL-18 (p=0.25) cytokines. While acute exercise with severity initiation of the activity of the inflammatory complex, with a significant increase in serum levels of IL-1β, IL-18 and, and expression of NLRP3 and TLR4 genes (p=0.01). Also moderate chronic aerobic exercise also significantly reduced the expression of NLRP3, TLR4 genes and serum levels of IL-1β, IL-18 cytokines (p=0.001). In the case of high chronic training, significant increases in expression of genes NLRP3, TLR4 and serum levels of IL-1β, IL-18 cytokines were observed (p=0.0001). Conclusion: It can be concluded that endurance chronic aerobic activity with moderate intensity is effective in decreasing the expression of the inflammasome and inflammation while acute aerobic activity with some intensities  had no effect.

کلیدواژه‌ها [English]

  • Aerobic exercise
  • Infalammasome
  • Inflammation
  • TLR4 gene expression
Booth, S., Florida-James, G. D., McFarlin, B. K., Spielmann, G., O’Connor, D. P., & Simpson, R. J. (2010). The impact of acute strenuous exercise on TLR2, TLR4 and HLA. DR expression on human blood monocytes induced by autologous serum. European Journal of Applied Physiology, 110(6), 1259-1268.

Cavalcante, P. A. M., Gregnani, M. F., Henrique, J. S., Ornellas, F. H., & Araújo, R. C. (2017). Aerobic but not resistance exercise can induce inflammatory pathways via toll-like 2 and 4: a systematic review. Sports Medicine-Open, 3(1), 42.

Fernandez-Gonzalo, R., De Paz, J. A., Rodriguez-Miguelez, P., Cuevas, M. J., & González-Gallego, J. (2012). Effects of eccentric exercise on toll-like receptor 4 signaling pathway in peripheral blood mononuclear cells. Journal of Applied Physiology, 112(12), 2011-2018.

Fernandez-Gonzalo, R., De Paz, J. A., Rodriguez-Miguelez, P., Cuevas, M. J., & González-Gallego, J. (2014). TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women. Mediators of Inflammation, 2014, 1-11.

Flynn, M. G., McFarlin, B. K., Phillips, M. D., Stewart, L. K., & Timmerman, K. L. (2003). Toll-like receptor 4 and CD14 mRNA expression are lower in resistive exercise-trained elderly women. Journal of Applied Physiology, 95(5), 1833-1842.

Gleeson, M., McFarlin, B., & Flynn, M. (2006). Exercise and Toll-like receptors. Exercise Immunology Review, 12(1), 34-53.

Jackson, A. S., & Pollock, M. L. (1978). Generalized equations for predicting body density of men. British Journal of Nutrition, 40(3), 497-504.

Lancaster, G. I., Khan, Q., Drysdale, P., Wallace, F., Jeukendrup, A. E., Drayson, M. T., & Gleeson, M. (2005). The physiological regulation of toll‐like receptor expression and function in humans. The Journal of Physiology, 563(3), 945-955.

Lee, W. J. (2011). IGF-I exerts an anti-inflammatory effect on skeletal muscle cells through down-regulation of TLR4 signaling. Immune Network, 11(4), 223-226.

Li, H., Miao, W., Ma, J., Xv, Z., Bo, H., Li, J., Ji, L. L. (2016). Acute exercise-induced mitochondrial stress triggers an inflammatory response in the myocardium via NLRP3 inflammasome activation with mitophagy. Oxidative Medicine and Cellular Longevity, 2016, 1-11.

Lust, J. A., Lacy, M. Q., Zeldenrust, S. R., Dispenzieri, A., Gertz, M. A., Witzig, T. E., … & Donovan, K. A. (2009). Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1β-induced interleukin 6 production and the myeloma proliferative component. Mayo Clinic Proceedings, 84(2), 114-122.

Ma, Y., He, M., & Qiang, L. (2013). Exercise therapy downregulates the overexpression of TLR4, TLR2, MyD88 and NF-κB after cerebral ischemia in rats. International Journal of Molecular Sciences, 14(2), 3718-3733.

Mardare, C., Krüger, K., Liebisch, G., Seimetz, M., Couturier, A., Ringseis, R,. Mooren, F. C. (2016). Endurance and resistance training affect high fat diet-induced increase of ceramides, inflammasome expression, and systemic inflammation in mice. Journal of Diabetes Research, 2016(7), 23-444.

Maverakis, E., Kim, K., Shimoda, M., Gershwin, M. E., Wilken, R., Raychaudhuri, S, Lebrilla, C. B. (2015). Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review. Journal of Autoimmunity, 57(3), 1-13.

McFarlin, B. K., Flynn, M. G., Campbell, W. W., Craig, B. A., Robinson, J. P., Stewart, L. K., Coen, P. M. (2006). Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 61(4), 388-393.

McFarlin, B. K., Flynn, M. G., Campbell, W. W., Stewart, L. K., & Timmerman, K. L. (2004). TLR4 is lower in resistance-trained older women and related to inflammatory cytokines. Medicine and science in Sports and Exercise, 36(11), 1876-1883.

Mejías-Peña, Y., Estébanez, B., Rodriguez-Miguelez, P., Fernandez-Gonzalo, R., Almar, M., de Paz, J. A., Cuevas, M. J. (2017). Impact of resistance training on the autophagy-inflammation-apoptosis crosstalk in elderly subjects. Aging (Albany NY), 9(2), 408.

Miao, E. A., Alpuche-Aranda, C. M., Dors, M., Clark, A. E., Bader, M. W., Miller, S. I., & Aderem, A. (2006). Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf. Nature Immunology, 7(6), 569.

Monda, V., Villano, I., Messina, A., Valenzano, A., Esposito, T., Moscatelli, F., Monda, M. (2017). Exercise modifies the gut microbiota with positive health effects. Oxidative Medicine and Cellular Longevity, 2017(5), 33-131.

Mori, M. A., Bezy, O., & Kahn, C. R. (2011). Metabolic syndrome: is Nlrp3 inflammasome a trigger or a target of insulin resistance? Circulation Research, 108(10), 1160-1162.

Oliveira, A. G., Carvalho, B. M., Tobar, N., Ropelle, E. R., Pauli, J. R., Bagarolli, R. A., … & Saud, M. J. (2011). Physical exercise reduces circulating lipopolysaccharide and toll–like receptor 4 activation and improves insulin signaling in tissues of diet-induced obesity rats. Diabetes, 60(3), 784-796.

Petersen, A. M. W., & Pedersen, B. K. (2005). The anti-inflammatory effect of exercise. Journal of Applied Physiology, 98(4), 1154-1162.

Rosa, J. C., Lira, F. S., Eguchi, R., Pimentel, G. D., Venâncio, D. P., Cunha, C. A., … & Oller do Nascimento, C. M. (2011). Exhaustive exercise increases inflammatory response via toll like receptor‐4 and NF‐κBp65 pathway in rat adipose tissue. Journal of cellular physiology, 226(6), 1604-1607.

Sansonetti, P. J., Phalipon, A., Arondel, J., Thirumalai, K., Banerjee, S., Akira, S., … & Zychlinsky, A. (2000). Caspase-1 activation of IL-1β and IL-18 are essential for Shigella flexneri–induced inflammation. Immunity, 12(5), 581-590.

Slattery, K., Bentley, D., & Coutts, A. J. (2015). The role of oxidative, inflammatory and neuroendocrinological systems during exercise stress in athletes: implications of antioxidant supplementation on physiological adaptation during intensified physical training. Sports Medicine, 45(4), 453-471.

Smith, A. M. A., Patrick, K., Heywood, W., Pitts, M. K., Richters, J., Shelley, J. M., ... & Ryall, R. (2012). Body mass index, sexual difficulties and sexual satisfaction among people in regular heterosexual relationships: a population‐based study. Internal Medicine Journal, 42(6), 641-651.

Stewart, L. K., Flynn, M. G., Campbell, W. W., Craig, B. A., Robinson, J. P., McFarlin, B. K., ... & Talbert, E. (2005). Influence of exercise training and age on CD14+ cell-surface expression of toll-like receptor 2 and 4. Brain, Behavior, and Immunity, 19(5), 389-397.

Takeda, K., & Akira, S. (2005). Toll-like receptors in innate immunity. International Immunology, 17(1), 1-14.

Terra, R., Silva, S. A. G. D., Pinto, V. S., & Dutra, P. M. L. (2012). Effect of exercise on immune system: response, adaptation and cell signaling. Revista Brasileira de Medicina do Esporte, 18(3), 208-214.

Wu, X. D., Zeng, K., Liu, W. L., Gao, Y. G., Gong, C. S., Zhang, C. X., & Chen, Y. Q. (2014). Effect of aerobic exercise on miRNA-TLR4 signaling in atherosclerosis. International Journal of Sports Medicine, 35(04), 344-350.

Zbinden-Foncea, H., Raymackers, J.-M., Deldicque, L., Renard, P., & Francaux, M. (2012). TLR2 and TLR4 activate p38 MAPK and JNK during endurance exercise in skeletal muscle. Medicine and Science in Sports and Exercise, 44(8), 1463-1472.