The miR-30a Negatively Regulates IL-17-Mediated Signal Transduction by Targeting Traf3ip2

J Interferon Cytokine Res. 2015 Nov;35(11):917-23. doi: 10.1089/jir.2014.0146. Epub 2015 Sep 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • Cell Line, Tumor
  • Cytokines / biosynthesis
  • Down-Regulation
  • Enzyme Activation / immunology
  • HeLa Cells
  • Humans
  • Inflammation / immunology
  • Interleukin-17 / immunology*
  • MAP Kinase Signaling System / immunology*
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / immunology
  • RNA, Messenger / genetics
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / biosynthesis*
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • Interleukin-17
  • MIRN30b microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Messenger
  • TRAF3IP2 protein, human
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
  • Mitogen-Activated Protein Kinases