TNF-α-induced MiR-155 Regulates IL-6 Signaling in Rheumatoid Synovial Fibroblasts

Overview

Journal BMC Res Notes

Publisher Biomed Central

Specialties Biology
General Medicine

Date 2017 Aug 16

PMID 28807007

Citations 24

Authors

Kiyoshi Migita

Nozomi Iwanaga

Yasumori Izumi

Chieko Kawahara

Kenji Kumagai

Tadashi Nakamura

Tomohiro Koga

Atsushi Kawakami

Affiliations

Soon will be listed here.

Abstract

Background: MicroRNAs (miRNAs) are important regulators of a variety of inflammatory mediators. The present study was undertaken to elucidate the role of miRNAs in the rheumatoid cytokine network.

Methods: We analyzed miRNA expression in rheumatoid synovial fibroblasts (RASFs). miRNA array-based screening was used to identify miRNAs differentially expressed between tumor necrosis factor-α (TNF-α)-activated RASFs and untreated RASFs. Transfection of RASFs with miR-155 was used to analyze the function of miR-155. Real-time polymerase chain reaction (PCR) was used to measure the levels of miR-155 in RASFs.

Results: miRNA microarray analysis revealed that miR-155-5p was the most highly induced miRNA in TNF-α-stimulated RASFs. TNF-α-induced miR-155 expression in RASFs was time-dependent and TNFα dose-dependent, whereas, IL-6 stimulation did not affect miR-155 expression in RASFs. Transfection of miR-155 mimics into RASFs resulted in the decrease JAK2/STAT3 phosphorylation in IL-6-treated RASFs.

Conclusions: The current results demonstrate that TNF-α modulated miRNA expressions in RASFs. Our data showed that miR-155, which is highly induced by TNF-α stimulation, inhibits IL-6-mediated JAK2/STAT3 activation in RASFs. These findings suggest that miR-155 contributes to the cross-regulation between TNF-α and IL-6-mediated inflammatory pathways in RA.

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References

Feldmann M, Brennan F, Maini R . Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996; 14:397-440. DOI: 10.1146/annurev.immunol.14.1.397. View

Luo X, Tsai L, Shen N, Yu D . Evidence for microRNA-mediated regulation in rheumatic diseases. Ann Rheum Dis. 2009; 69 Suppl 1:i30-36. DOI: 10.1136/ard.2009.117218. View

Choy E . Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012; 51 Suppl 5:v3-11. DOI: 10.1093/rheumatology/kes113. View

Ceppi M, Pereira P, Dunand-Sauthier I, Barras E, Reith W, Santos M . MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci U S A. 2009; 106(8):2735-40. PMC: 2650335. DOI: 10.1073/pnas.0811073106. View

Hashizume M, Hayakawa N, Mihara M . IL-6 trans-signalling directly induces RANKL on fibroblast-like synovial cells and is involved in RANKL induction by TNF-alpha and IL-17. Rheumatology (Oxford). 2008; 47(11):1635-40. DOI: 10.1093/rheumatology/ken363. View

Jonas S, Izaurralde E . Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet. 2015; 16(7):421-33. DOI: 10.1038/nrg3965. View

Connell L, McInnes I . New cytokine targets in inflammatory rheumatic diseases. Best Pract Res Clin Rheumatol. 2006; 20(5):865-78. DOI: 10.1016/j.berh.2006.05.011. View

Ammari M, Jorgensen C, Apparailly F . Impact of microRNAs on the understanding and treatment of rheumatoid arthritis. Curr Opin Rheumatol. 2013; 25(2):225-33. DOI: 10.1097/BOR.0b013e32835d8385. View

Vigorito E, Kohlhaas S, Lu D, Leyland R . miR-155: an ancient regulator of the immune system. Immunol Rev. 2013; 253(1):146-57. DOI: 10.1111/imr.12057. View

10.

Deon D, Ahmed S, Tai K, Scaletta N, Herrero C, Lee I . Cross-talk between IL-1 and IL-6 signaling pathways in rheumatoid arthritis synovial fibroblasts. J Immunol. 2001; 167(9):5395-403. DOI: 10.4049/jimmunol.167.9.5395. View

11.

Churov A, Oleinik E, Knip M . MicroRNAs in rheumatoid arthritis: altered expression and diagnostic potential. Autoimmun Rev. 2015; 14(11):1029-37. DOI: 10.1016/j.autrev.2015.07.005. View

12.

Wang P, Hou J, Lin L, Wang C, Liu X, Li D . Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1. J Immunol. 2010; 185(10):6226-33. DOI: 10.4049/jimmunol.1000491. View

13.

Elton T, Selemon H, Elton S, Parinandi N . Regulation of the MIR155 host gene in physiological and pathological processes. Gene. 2012; 532(1):1-12. DOI: 10.1016/j.gene.2012.12.009. View

14.

Yoshimura A, Naka T, Kubo M . SOCS proteins, cytokine signalling and immune regulation. Nat Rev Immunol. 2007; 7(6):454-65. DOI: 10.1038/nri2093. View

15.

Fonseca J, Santos M, Canhao H, Choy E . Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev. 2009; 8(7):538-42. DOI: 10.1016/j.autrev.2009.01.012. View

16.

Heinrich P, Behrmann I, Haan S, Hermanns H, Muller-Newen G, Schaper F . Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J. 2003; 374(Pt 1):1-20. PMC: 1223585. DOI: 10.1042/BJ20030407. View

17.

Stanczyk J, Leslie Pedrioli D, Brentano F, Sanchez-Pernaute O, Kolling C, Gay R . Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 2008; 58(4):1001-9. DOI: 10.1002/art.23386. View

18.

McInnes I, Schett G . The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011; 365(23):2205-19. DOI: 10.1056/NEJMra1004965. View

19.

Kurowska-Stolarska M, Alivernini S, Ballantine L, Asquith D, Millar N, Gilchrist D . MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci U S A. 2011; 108(27):11193-8. PMC: 3131377. DOI: 10.1073/pnas.1019536108. View

20.

Feldmann M, Maini R . Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?. Annu Rev Immunol. 2001; 19:163-96. DOI: 10.1146/annurev.immunol.19.1.163. View