Role of miR-146a in the Regulation of Inflammation in an In Vitro Model of Graves' Orbitopathy
- Authors
- Jang, Sun Young; Chae, Min Kyung; Lee, Joon H.; Lee, Eun Jig; Yoon, Jin Sook
- Issue Date
- Aug-2016
- Publisher
- Association for Research in Vision and Ophthalmology
- Keywords
- miR-146a; inflammation; Graves' orbitopathy
- Citation
- Investigative Ophthalmology and Visual Science, v.57, no.10, pp 4027 - 4034
- Pages
- 8
- Journal Title
- Investigative Ophthalmology and Visual Science
- Volume
- 57
- Number
- 10
- Start Page
- 4027
- End Page
- 4034
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/8895
- DOI
- 10.1167/iovs.16-19213
- ISSN
- 0146-0404
1552-5783
- 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 1 beta (IL-1 beta) on miR-146a expression were analyzed in orbital fibroblasts by qPCR. To investigate the molecular mechanism underlying IL-1 beta-induced miR-146a expression, the effects of inhibitors of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), mitogen-activated 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-1 beta-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 1 beta induced a time-and concentration-dependent increase in miR-146a expression. Interleukin 1 beta (10 ng/mL, 16 hours) induced an approximately 17.5-fold increase in miR-146 expression. The increase in miR-146a expression by IL-1 beta was significantly inhibited by NF-kappa B, 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-1 beta-induced miR146 expression, independent t-test). Interleukin 1 beta-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.
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