Irisin protects female mice with LPS-induced endometritis through the AMPK/NF-κB pathway

Document Type : Original Article

Authors

1 Zhejiang University Mingzhou Hospital, Ningbo, 315000, China

2 Department of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, 315000, China

Abstract

Objective(s): This research was designed to determine the role of irisin in lipopolysaccharide (LPS)-induced endometritis in female mice.
Materials and Methods: Animals were randomly assigned into sham, sham + irisin, LPS, LPS + irisin (0.1, 1, 10 μg/kg), and LPS + irisin + compound C groups. Histological features and expression of AMPK, NF-κB, inflammatory mediators, and oxidative stress markers were compared among different groups.
Results: The results showed that LPS resulted in obvious uterus damage, meanwhile, the inflammatory mediators (COX-2, iNOS, IL-1β, IL-6, and TNF-α), as well as NF-κB in the uterine tissue, were significantly increased and the level of adenosine monophosphate-activated protein kinase (AMPK) was reduced. Nevertheless, pretreatment with irisin reversed the phenomena caused by LPS. Interestingly, compound C (AMPK inhibitor) abolished irisin’s effects on the uterus, which suggested that irisin’s beneficial function was achieved through regulating the AMPK-NF-κB pathway. Moreover, LPS-induced alterations of oxidative factors (MnSOD, GSH, and MDA) were reversed significantly by pretreatment with irisin. This data indicated irisin’s beneficial function was also related to antioxidation besides anti-inflammation.  
Conclusion: Our study implies that irisin is a potential therapeutic agent for endometritis.

Keywords

References

1. Gautam G, Nakao T, Yusuf M, Koike K. Prevalence of endometritis during the postpartum period and its impact on subsequent reproductive performance in two Japanese dairy herds. Anim Reprod Sci 2009; 116:175-187.
2. Park HJ, Kim YS, Yoon TK, Lee WS. Chronic endometritis and infertility. Clin Exp Reprod Med 2016; 43:185-192.
3. Gilbert RO, Shin ST, Guard CL, Erb HN, Frajblat M. Prevalence of endometritis and its effects on reproductive performance of dairy cows. Theriogenology 2005; 64:1879-1888.
4. Jiang K, Chen X, Zhao G, Wu H, Mi J, Qiu C, et al. IFN-tau Plays an Anti-Inflammatory Role in Staphylococcus aureus-Induced Endometritis in Mice Through the Suppression of NF-kappaB Pathway and MMP9 Expression. J Interferon Cytokine Res 2017; 37:81-89.
5. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481:463-468.
6. Peterson JM, Mart R, Bond CE. Effect of obesity and exercise on the expression of the novel myokines, Myonectin and Fibronectin type III domain containing 5. Peer J 2014; 2:e605.
7. Ren YF, Wang MZ, Bi JB, Zhang J, Zhang L, Liu WM, et al. Irisin attenuates intestinal injury, oxidative and endoplasmic reticulum stress in mice with L-arginine-induced acute pancreatitis. World J Gastroenterol 2019; 25:6653-6667.
8. Narayanan SA, Metzger CE, Bloomfield SA, Zawieja DC. Inflammation-induced lymphatic architecture and bone turnover changes are ameliorated by irisin treatment in chronic inflammatory bowel disease. FASEB J 2018; 32:4848-4861.
9. Zhao YT, Wang J, Yano N, Zhang LX, Wang H, Zhang S, et al. Irisin promotes cardiac progenitor cell-induced myocardial repair and functional improvement in infarcted heart. J Cell Physiol 2019; 234:1671-1681.
10. Pignataro P, Dicarlo M, Zerlotin R, Zecca C, Dell’Abate MT, Buccoliero C, et al. FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective. Int J Mol Sci 2021; 22:1605.
11. Csaki C, Mobasheri A, Shakibaei M. Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis. Arthritis Res Ther 2009; 11:R165.
12. Zhang D, Xie T, Leung PS. Irisin Ameliorates Glucolipotoxicity-Associated beta-Cell Dysfunction and Apoptosis via AMPK Signaling and Anti-Inflammatory Actions. Cell Physiol Biochem 2018; 51:924-937.
13. Wang K, Li H, Wang H, Wang JH, Song F, Sun Y. Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes. Mediators Inflamm 2018; 2018:9070341.
14. Tortorella C, Piazzolla G, Matteo M, Pinto V, Tinelli R, Sabba C, et al. Interleukin-6, interleukin-1beta, and tumor necrosis factor alpha in menstrual effluents as biomarkers of chronic endometritis. Fertil Steril 2014; 101:242-247.
15. Tiwari A, Singh P, Jaitley P, Sharma S, Prakash A, Mandil R, et al. Eucalyptus robusta leaves methanolic extract suppresses inflammatory mediators by specifically targeting TLR4/TLR9, MPO, COX2, iNOS and inflammatory cytokines in experimentally-induced endometritis in rats. J Ethnopharmacol 2018; 213:149-158.
16. Wang F, Chen S, Deng L, Chen L, Huang Y, Tian M, et al. Protective Effects of Astragaloside IV against LPS-Induced Endometritis in Mice through Inhibiting Activation of the NF-kappaB, p38 and JNK Signaling Pathways. Molecules 2019; 24.
17. Zhang H, Wu ZM, Yang YP, Shaukat A, Yang J, Guo YF, et al. Catalpol ameliorates LPS-induced endometritis by inhibiting inflammation and TLR4/NF-kappaB signaling. J Zhejiang Univ Sci B 2019; 20:816-827.
18. MacMillan-Crow LA, Thompson JA. Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch Biochem Biophys 1999; 366:82-88.
19. Kimura F, Takebayashi A, Ishida M, Nakamura A, Kitazawa J, Morimune A, et al. Review: Chronic endometritis and its effect on reproduction. J Obstet Gynaecol Res 2019; 45:951-960.
20. Li W, Fu K, Lv X, Wang Y, Wang J, Li H, et al. Lactoferrin suppresses lipopolysaccharide-induced endometritis in mice via down-regulation of the NF-kappaB pathway. Int Immunopharmacol 2015; 28:695-699.
21. Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol 2009; 1:a001651.
22. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 2013; 13:159-175.
23. Li R, Maimai T, Yao H, Liu X, He Z, Xiao C, et al. Protective effects of polydatin on LPS-induced endometritis in mice. Microb Pathog 2019; 137:103720.
24. Odusanwo O, Chinthamani S, McCall A, Duffey ME, Baker OJ. Resolvin D1 prevents TNF-alpha-mediated disruption of salivary epithelial formation. Am J Physiol Cell Physiol 2012; 302:C1331-1345.
25. Wu H, Zhao G, Jiang K, Li C, Qiu C, Deng G. Engeletin Alleviates Lipopolysaccharide-Induced Endometritis in Mice by Inhibiting TLR4-mediated NF-kappaB Activation. J Agric Food Chem 2016; 64:6171-6178.
26. Wang S, Pan J. Irisin ameliorates depressive-like behaviors in rats by regulating energy metabolism. Biochem Biophys Res Commun 2016; 474:22-28.
27. Minghetti L, Levi G. Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog Neurobiol 1998; 54:99-125.
28. Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005; 15:316-328.
29. Sahin S, Ozakpinar OB, Ak K, Eroglu M, Acikel M, Tetik S, et al. The protective effects of tacrolimus on rat uteri exposed to ischemia-reperfusion injury: A biochemical and histopathologic evaluation. Fertil Steril 2014; 101:1176-1182.
30. Jiang PY, Zhu XJ, Zhang YN, Zhou FF, Yang XF. Protective effects of apigenin on LPS-induced endometritis via activating Nrf2 signaling pathway. Microb Pathog 2018; 123:139-143.
Iranian Journal of Basic Medical Sciences
Volume 24, Issue 9
September 2021
Pages 1247-1253

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