MicroRNA-155 inhibitor ameliorates collagen-induced arthritis by modulating the phenotype of pro-inflammatory macrophages in a mouse model

  • Yuanliang Chen Department of Orthopaedic Surgery, Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People’s Hospital, Hainan 570311, China.
  • Hong Sung Min Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China.
  • Yongbai Wan Department of Orthopaedic Surgery, Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People’s Hospital, Hainan 570311, China.
  • Chaolai Jiang Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China.
  • Xiaowei Yu 1 Department of Orthopaedic Surgery, Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People’s Hospital, Hainan 570311, China. 2 Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China.
Keywords: MicroRNA-155, Arthritis, Collagen-induced arthritis, Macrophages, Macrophage polarization

Abstract

Background: The present study aims to investigate the roles of microRNA-155 in collagen-induced arthritis (CIA) and its underlying mechanisms.

Methods: CIA mouse model was established and miR155 inhibitor was intravenously injected. In in vitro studies, bone marrow-derived macrophages (BMDMs) were induced into M1 macrophages followed by the treatment of miR155 inhibitor. Quantitative reverse transcription PCR (RT-qPCR) was applied to determine the mRNA expressions. Flow cytometry was applied to determine the frequency of M1 or M2 macrophages. Western blotting was determined to detect protein expressions. Enzyme-linked immunosorbent assay (ELISA) was applied to determine the levels of inflammatory cytokines and anti-collagen antibody.  

Results: The levels of miR155 were increased in macrophages from rheumatoid arthritis (RA) patients and M1 macrophages. The treatment of miR155 inhibitor decreased inflammatory cytokines in M1 macrophages. Besides, treatment of miR155 inhibitors promoted the differentiation of M0 macrophages into M2 macrophages. In vivo studies demonstrated that the treatment of miR155 inhibitors ameliorated the RA symptoms by decreasing inflammatory cytokines in the CIA mouse model. Treatment of miR155 also resulted in a decrease of M1 macrophage biomarker and an increase of M2 macrophage biomarker.

Conclusion: microRNA-155 inhibitor ameliorates RA symptoms in part by regulating macrophage phenotypes.

Downloads

Download data is not yet available.

References

Firestein GS. Evolving concepts of rheumatoid arthritis. Nature. 2003;423(6937):356-61.

Decker JL, Malone DG, Haraoui B, Wahl SM, Schrieber L, Klippel JH, et al. NIH conference. Rheumatoid arthritis: evolving concepts of pathogenesis and treatment. Ann Intern Med. 1984;101(6):810-24.

Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005;4(3):130-6.

Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001;344(12):907-16.

Ma Y, Pope RM. The role of macrophages in rheumatoid arthritis. Curr Pharm Des. 2005;11(5):569-80.

Wang Y, Han CC, Cui D, Li Y, Ma Y, Wei W. Is macrophage polarization important in rheumatoid arthritis? Int Immunopharmacol. 2017;50:345-52.

Tardito S, Martinelli G, Soldano S, Paolino S, Pacini G, Patane M, et al. Macrophage M1/M2 polarization and rheumatoid arthritis: a systematic review. Autoimmun Rev. 2019;18(11):102397.

Siouti E, Andreakos E. The many facets of macrophages in rheumatoid arthritis. Biochem Pharmacol. 2019;165:152-69.

Liu G, Abraham E. MicroRNAs in immune response and macrophage polarization. Arterioscler Thromb Vasc Biol. 2013;33(2):170-7.

Wu XQ, Dai Y, Yang Y, Huang C, Meng XM, Wu BM, et al. Emerging role of microRNAs in regulating macrophage activation and polarization in immune response and inflammation. Immunology. 2016;148(3):237-48.

Essandoh K, Li Y, Huo J, Fan GC. MiRNA-mediated macrophage polarization and its potential role in the regulation of inflammatory response. Shock. 2016;46(2):122-31.

Bluml S, Bonelli M, Niederreiter B, Puchner A, Mayr G, Hayer S, et al. Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum. 2011;63(5):1281-8.

Su LC, Huang AF, Jia H, Liu Y, Xu WD. Role of microRNA-155 in rheumatoid arthritis. Int J Rheum Dis. 2017;20(11):1631-7.

Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther. 2008;10(4):R101.

Weischenfeldt J, Porse B. Bone marrow-derived macrophages (BMM): isolation and applications. CSH Protoc. 2008:pdb prot5080.

Liu C, Zhao J, Liu Y, Huang Y, Shen Y, Wang J, et al. A novel pentacyclic triterpenoid, Ilexgenin A, shows reduction of atherosclerosis in apolipoprotein E deficient mice. Int Immunopharmacol. 2016;40:115-24.

Yang H, Wang J, Fan JH, Zhang YQ, Zhao JX, Dai XJ, et al. Ilexgenin A exerts anti-inflammation and anti-angiogenesis effects through inhibition of STAT3 and PI3K pathways and exhibits synergistic effects with Sorafenib on hepatoma growth. Toxicol Appl Pharmacol. 2017;315:90-101.

Maruotti N, Cantatore FP, Crivellato E, Vacca A, Ribatti D. Macrophages in rheumatoid arthritis. Histol Histopathol. 2007;22(5):581-6.

Ridgley LA, Anderson AE, Pratt AG. What are the dominant cytokines in early rheumatoid arthritis? Curr Opin Rheumatol. 2018;30(2):207-14.

Zhang A, Lee YC. Mechanisms for joint pain in rheumatoid arthritis (RA): from cytokines to central sensitization. Curr Osteoporos Rep. 2018;16(5):603-10.

Udalova IA, Mantovani A, Feldmann M. Macrophage heterogeneity in the context of rheumatoid arthritis. Nat Rev Rheumatol. 2016;12(8):472-85.

Soler Palacios B, Estrada-Capetillo L, Izquierdo E, Criado G, Nieto C, Municio C, et al. Macrophages from the synovium of active rheumatoid arthritis exhibit an activin A-dependent pro-inflammatory profile. J Pathol. 2015;235(3):515-26.

Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol. 2011;11(11):750-61.

Jablonski KA, Amici SA, Webb LM, Ruiz-Rosado Jde D, Popovich PG, Partida-Sanchez S, et al. Novel markers to delineate murine M1 and M2 macrophages. PLoS One. 2015;10(12):e0145342.

Aron-Wisnewsky J, Tordjman J, Poitou C, Darakhshan F, Hugol D, Basdevant A, et al. Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab. 2009;94(11):4619-23.

Weisser SB, McLarren KW, Kuroda E, Sly LM. Generation and characterization of murine alternatively activated macrophages. Methods Mol Biol. 2013;946:225-39.

Kaplan M, Shur A, Tendler Y. M1 Macrophages but not M2 macrophages are characterized by upregulation of CRP expression via activation of NFkappaB: a possible role for Ox-LDL in macrophage polarization. Inflammation. 2018;41(4):1477-87.

Yang GH, Zhang C, Wang N, Meng Y, Wang YS. Anacardic acid suppresses fibroblast-like synoviocyte proliferation and invasion and ameliorates collagen-induced arthritis in a mouse model. Cytokine. 2018;111:350-6.

Wang J, Li Y, Li L, Yang J, Kopecek J. Exploration and evaluation of therapeutic efficacy of drug-free macromolecular therapeutics in collagen-induced rheumatoid arthritis mouse model. Macromol Biosci. 2020:e1900445.

Published
2021-09-18
How to Cite
ChenY., MinH. S., WanY., JiangC., & YuX. (2021). MicroRNA-155 inhibitor ameliorates collagen-induced arthritis by modulating the phenotype of pro-inflammatory macrophages in a mouse model. STEMedicine, 2(8), e105. https://doi.org/10.37175/stemedicine.v2i8.105
Section
Research articles