Combined Training Improves the Expression Profile of Inflammation-associated Antimicrobial Peptides, MicroRNAs, and TLR-4 in Patients with Multiple Sclerosis
Some antimicrobial peptides (AMPs), microRNAs (miRs), and Toll-like receptor 4 (TLR-4) are involved in autoimmune diseases, which may be affected by exercise training. The purpose of this study was to investigate the effect of an eight-week combined exercise training (aerobic and resistance) on the expression of inflammatory factors, including, human beta-defensin-2 (hBD-2), cathelicidin (LL-37), TLR-4, miR-23b, miR-155, and miR-326 in women with relapsing and remitting multiple sclerosis (RRMS), which has not been investigated yet.
Twenty-three women (20-40 years) with RRMS were randomized into the combined training (CT) and control (CON) groups. The CT group subjects completed eight weeks of supervised CT using a treadmill and stationary bicycle for aerobic exercise and weight machines for resistance exercise. The expression levels of hBD-2, LL-37, TLR-4, miR-23b, miR-155, and miR-326 were measured by real-time polymerase chain reaction (RT-PCR) at the baseline and end of the study.
Although the expression of hBD-2 and miR-23b decreased in both CT and CON groups, the reduction was lower in the CT group than in the CON group (p=0.001). The expression of LL-37 in the CT group remained unchanged, but that of the CON group increased; thus, the between-group difference was significant. Although the TLR-4, miR-155, and miR-326 expression increased in both groups compared to the baseline, the increase in the CT group was lower than the CON group.
Our results showed that the combined training might improve inflammatory symptoms by affecting the expression of some AMPs, miRs, and TLR-4 in patients with relapsing and remitting multiple sclerosis.
2. Comabella M, Khoury SJ. Immunopathogenesis of multiple sclerosis. Clin Immunolo. 2012;142(1):2-8.
3. Fortune J, Norris M, Stennett AM, Kilbride C, Lavelle G, Hendrie W, et al. Correlates of objectively measured physical activity in persons with multiple sclerosis. Physiotherapy. 2019;105:e138-e9.
4. Motl RW, Sandroff BM, Benedict RH. Cognitive dysfunction and multiple sclerosis: developing a rationale for considering the efficacy of exercise training. Mult Scler. 2011;17(9):1034-40.
5. Guillamo E, Cobo-Calvo A, Oviedo GR, Travier N, Alamo J, Nino-Mendez OA, et al. Feasibility and Effects of Structured Physical Exercise Interventions in Adults with Relapsing-Remitting Multiple Sclerosis: A Pilot Study. J Sports sci Med. 2018;17(3):426-36.
6. Sangelaji B, Kordi M, Banihashemi F, Nabavi SM, Khodadadeh S, Dastoorpoor M. A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: A randomized clinical trial. Iranian J Neurol. 2016;15(3):111-20.
7. Golzari Z, Shabkhiz F, Soudi S, Kordi MR, Hashemi SM. Combined exercise training reduces IFN-gamma and IL-17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis. Inter Immunopharmacol. 2010;10(11):1415-9.
8. Deckx N, Wens I, Nuyts AH, Hens N, De Winter BY, Koppen G, et al. 12 Weeks of Combined Endurance and Resistance Training Reduces Innate Markers of Inflammation in a Randomized Controlled Clinical Trial in Patients with Multiple Sclerosis. Med Inflamm. 2016;2016:6789276.
9. Williams WM, Castellani RJ, Weinberg A, Perry G, Smith MA. Do beta-defensins and other antimicrobial peptides play a role in neuroimmune function and neurodegeneration? Scientific World J. 2012;2012:905785.
10. Auvynet C, Rosenstein Y. Multifunctional host defense peptides: antimicrobial peptides, the small yet big players in innate and adaptive immunity. FEBS J. 2009;276(22):6497-508.
11. Mookherjee N, Hancock RE. Cationic host defence peptides: innate immune regulatory peptides as a novel approach for treating infections. Cell Mol life. 2007;64(7-8):922-33.
12. Dombrowski Y, Schauber J. Cathelicidin LL-37: a defense molecule with a potential role in psoriasis pathogenesis. Exp Dermatol. 2012;21(5):327-30.
13. Kahlenberg JM, Kaplan MJ. Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease. J Immunol. 2013;191(10):4895-901.
14. Alcayaga-Miranda F, Cuenca J, Khoury M. Antimicrobial Activity of Mesenchymal Stem Cells: Current Status and New Perspectives of Antimicrobial Peptide-Based Therapies. Front Immunol. 2017;8(3):39-42.
15. Duits LA, Ravensbergen B, Rademaker M, Hiemstra PS, Nibbering PH. Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology. 2002;106(4):517-25.
16. Shabgah AG, Fattahi E, Shahneh FZ. Interleukin-17 in human inflammatory diseases. Postepy Dermatol Alergol. 2014;31(4):256-61.
17. Svensson D, Nebel D, Nilsson B-O. Vitamin D3 modulates the innate immune response through regulation of the hCAP-18/LL-37 gene expression and cytokine production. Inflamm Res. 2016;65(1):25-32.
18. Scott MG, Davidson DJ, Gold MR, Bowdish D, Hancock RE. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol. 2002;169(7):3883-91.
19. Shirvani H, Soleimani M, Sanayinasab H, Rahmati-Ahmadabad S. A Review on the Effect of Exercise on Obesity by Modulating the Immune System and Toll-Like Receptors. J Military Med. 2018;20(5):456-75.
20. Leitner GR, Wenzel TJ, Marshall N, Gates EJ, Klegeris A. Targeting toll-like receptor 4 to modulate neuroinflammation in central nervous system disorders. Expert Opin Ther Targets. 2019;23(10):865-82.
21. Arenas-Padilla M, Mata-Haro V. Regulation of TLR signaling pathways by microRNAs: implications in inflammatory diseases. Cent Eur J Immunol. 2018;43(4):482-9.
22. Murugaiyan G, Beynon V, Mittal A, Joller N, Weiner HL. Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis. J Immunol. 2011;187(5):2213-21.
23. Thamilarasan M, Koczan D, Hecker M, Paap B, Zettl UK. MicroRNAs in multiple sclerosis and experimental autoimmune encephalomyelitis. Autoimmun Rev. 2012;11(3):174-9.
24. de Faria O, Jr., Moore CS, Kennedy TE, Antel JP, Bar-Or A, Dhaunchak AS. MicroRNA dysregulation in multiple sclerosis. Frontiers in genetics. 2012;3:311.
25. Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S, et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol. 2009;10(12):1252-9.
26. Garo LP, Murugaiyan G. Contribution of MicroRNAs to autoimmune diseases. Cell Mol life Sci. 2016;73(10):2041-51.
27. Wei T, Cong X, Wang XT, Xu XJ, Min SN, Ye P, et al. Interleukin-17A promotes tongue squamous cell carcinoma metastasis through activating miR-23b/versican pathway. Oncotarget. 2017;8(4):6663-80.
28. Liu X, Ni S, Li C, Xu N, Chen W, Wu M, et al. Circulating microRNA-23b as a new biomarker for rheumatoid arthritis. Gene. 2019;712(21):143911.
29. O'Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA, et al. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity. 2010;33(4):607-19.
30. Jurkovicova D, Magyerkova M, Kulcsar L, Krivjanska M, Krivjansky V, Gibadulinova A, et al. miR-155 as a diagnostic and prognostic marker in hematological and solid malignancies. Neoplasma. 2014;61(3):241-51.
31. Junker A, Krumbholz M, Eisele S, Mohan H, Augstein F, Bittner R, et al. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain. 2009;132(Pt 12):3342-52.
32. Wlodarczyk M, Druszczynska M, Fol M. Trained Innate Immunity Not Always Amicable. Int J Mol Sci. 2019;20(10):34-41.
33. Bayraktar R, Bertilaccio MTS, Calin GA. The Interaction Between Two Worlds: MicroRNAs and Toll-Like Receptors. Front Immunol. 2019;10(2):1053-5.
34. Usui T, Yoshikawa T, Orita K, Ueda SY, Katsura Y, Fujimoto S, et al. Changes in salivary antimicrobial peptides, immunoglobulin A and cortisol after prolonged strenuous exercise. Eur J Appl Physiol. 2011;111(9):2005-14.
35. Eda N, Shimizu K, Suzuki S, Tanabe Y, Lee E, Akama T. Effects of yoga exercise on salivary beta-defensin 2. Eur J Appl Physiol. 2013;113(10):2621-7.
36. Gillum TL, Kuennen MR, Castillo MN, Williams NL, Jordan-Patterson AT. Exercise, but not acute sleep loss, increases salivary antimicrobial protein secretion. J Strength Cond Res. 2015;29(5):1359-66.
37. Davison G, Allgrove J, Gleeson M. Salivary antimicrobial peptides (LL-37 and alpha-defensins HNP1-3), antimicrobial and IgA responses to prolonged exercise. Eur J Appl Physiol. 2009;106(2):277-84.
38. Child ML, Melanie; and Gleeson, Michael. Effects of Two Weeks of High-intensity Interval Training (HIIT) on Monocyte TLR2 and TLR4 Expression in High BMI Sedentary Men. Int J Exerc Sci. 2013;6(1):45-6.
39. Stewart LK, Flynn MG, Campbell WW, Craig BA, Robinson JP, McFarlin BK, et al. Influence of exercise training and age on CD14+ cell-surface expression of toll-like receptor 2 and 4. Brain Behav Immun. 2005;19(5):389-97.
40. Robinson E, Durrer C, Simtchouk S, Jung ME, Bourne JE, Voth E, et al. Short-term high-intensity interval and moderate-intensity continuous training reduce leukocyte TLR4 in inactive adults at elevated risk of type 2 diabetes. J Appl Physiol. 2015;119(5):508-16.
41. Flynn MG, McFarlin BK, Phillips MD, Stewart LK, Timmerman KL. Toll-like receptor 4 and CD14 mRNA expression are lower in resistive exercise-trained elderly women. J Appl Physiol. 2003;95(5):1833-42.
42. Olesen J, Ringholm S, Nielsen MM, Brandt CT, Pedersen JT, Halling JF, et al. Role of PGC-1alpha in exercise training- and resveratrol-induced prevention of age-associated inflammation. Exp Gerontol. 2013;48(11):1274-84.
43. Moylan S, Eyre HA, Maes M, Baune BT, Jacka FN, Berk M. Exercising the worry away: how inflammation, oxidative and nitrogen stress mediates the beneficial effect of physical activity on anxiety disorder symptoms and behaviours. Neurosci Biobehav Rev. 2013;37(4):573-84.
44. Radom-Aizik S, Zaldivar F, Jr., Leu SY, Adams GR, Oliver S, Cooper DM. Effects of exercise on microRNA expression in young males peripheral blood mononuclear cells. Clin Transl Sci. 2012;5(1):32-8.
45. Kanterman J, Sade-Feldman M, Baniyash M. New insights into chronic inflammation-induced immunosuppression. Seminars in cancer biology. 2012;22(4):307-18.
46. Kunz H, Bishop NC, Spielmann G, Pistillo M, Reed J, Ograjsek T, et al. Fitness level impacts salivary antimicrobial protein responses to a single bout of cycling exercise. Eur J Appl Physiol. 2015;115(5):1015-27.
47. Agier J, Brzezinska-Blaszczyk E, Zelechowska P, Wiktorska M, Pietrzak J, Rozalska S. Cathelicidin LL-37 Affects Surface and Intracellular Toll-Like Receptor Expression in Tissue Mast Cells. J Immunol Res. 2018;2018:7357162.
48. Li Y, Zhang H, Wang Y. Tai Chi Ameliorates Coronary Heart Disease by Affecting Serum Levels of miR-24 and miR-155. Front Physiol. 2019;10:587.
49. Alizadeh S, Isanejad A, Sadighi S, Khalighfard S, Alizadeh AM. Effect of a high-intensity interval training on serum microRNA levels in women with breast cancer undergoing hormone therapy. A single-blind randomized trial. Ann Phys Rehabil Med. 2019;62(5):329-35.
50. Schwarz NA, McKinley-Barnard SK, Blahnik ZJ. Effect of Bang(R) Pre-Workout Master Blaster(R) combined with four weeks of resistance training on lean body mass, maximal strength, mircoRNA expression, and serum IGF-1 in men: a randomized, double-blind, placebo-controlled trial. J Int Soc Sports Nutr. 2019;16(1):54.
|Issue||Vol 20 No 4 (2021)|
|Antimicrobial cationic peptides Circuit-based exercise Inflammation Multiple sclerosis MicroRNAs|
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