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The miR-30a Negatively Regulates IL-17-Mediated Signal Transduction by Targeting Traf3ip2
Qun Wan1, Zhuo Zhou2, Shiping Ding1,3,2
11 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Medical College, Zhejiang University , Hangzhou, Zhejiang Province, People's Republic of China .
Abstract:
Interleukin-17 (IL-17) has been proved to be involved in the pathogenesis of several autoimmune diseases, including lupus, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. The regulation of IL-17 signal transduction is less studied. miR-30a has been identified to be downregulated in these human autoimmune diseases and their related animal models. However, how it functions in IL-17-mediated inflammation and the pathogenesis of these diseases remain unknown. In this study, we showed that miR-30a inhibits IL-17-mediated NF-κB and MAPK activation, leading to the reduced production of inflammatory cytokines and chemokines. miR-30a also reduced mRNA stability triggered by IL-17 stimulation. These suppressive effects of miR-30a were mediated by directly targeting Traf3ip2 mRNA (coding for Act1). Thus, we concluded that the downregulation of miR-30a in autoimmune diseases may exacerbate IL-17-mediated inflammation, which may serve as a potential target for the therapy of these diseases.
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