Role of miR-146a in the regulation of inflammation in an in vitro model of graves’ orbitopathy

Sun Young Jang, Min Kyung Chae, Joon H. Lee, Eun Jig Lee, Jin Sook Yoon

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

PURPOSE. To investigate the role of microRNA 146a (miR-146a) in the regulation of inflammation in an in vitro model of Graves’ orbitopathy (GO). METHODS. The level of miR-146a expression in orbital adipose tissue was compared between GO and non-GO by quantitative real-time PCR (qPCR). The effects of interleukin 1β (IL-1β) on miR-146a expression were analyzed in orbital fibroblasts by qPCR. To investigate the molecular mechanism underlying IL-1β -induced miR-146a expression, the effects of inhibitors of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogenactivated protein kinase/extracellular signal-regulated kinases (MEK)-1/2, c-Jun N-terminal kinases (JNK)-1/2, p38 MAP kinase, and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) were analyzed. The effects of miR-146a mimics and inhibitors on IL-1β -induced IL-6 release were examined by ELISA and Western blotting. RESULTS. The level of miR-146a expression was significantly higher in GO orbital adipose tissue than in non-GO (P = 0.032). Interleukin 1b induced a time- and concentration-dependent increase in miR-146a expression. Interleukin 1β (10 ng/mL, 16 hours) induced an approximately 17.5-fold increase in miR-146 expression. The increase in miR-146a expression by IL-1β was significantly inhibited by NF-κB, JNK-1/2, and PI3K inhibitors (1.94 ± 0.25, 5.28 ± 0.34 and 9.73 ± 2.32-fold, respectively, P < 0.05 compared with IL-1β -induced miR- 146 expression, independent t-test). Interleukin 1β -induced IL-6 protein production was further decreased by miR-146a mimics, but not by inhibitors of miR-146a. CONCLUSIONS. MicroRNA 146a was upregulated by inflammatory stress in orbital fibroblasts. Our results indicated that miR-146a had a positive effect on the anti-inflammatory process. MicroRNA 146a may play a role in the regulation of inflammation in orbital fibroblasts, and may participate in the pathogenesis of GO.

Original languageEnglish
Article number05
Pages (from-to)4027-4034
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number10
DOIs
Publication statusPublished - 2016 Aug 1

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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