MicroRNA-93 inhibits inflammatory cytokine production in LPS-stimulated murine macrophages by targeting IRAK4

FEBS Lett. 2014 May 2;588(9):1692-8. doi: 10.1016/j.febslet.2014.03.013. Epub 2014 Mar 15.

Abstract

Endotoxin-induced uveitis (EIU) is an animal model of acute ocular inflammation for the study of human endogenous anterior uveitis. The mechanisms accounting for the development of ocular inflammation remain hazy. MicroRNAs (mi-RNAs) have been proposed as novel regulators of inflammation. It remains unclear whether a microRNA-mediated regulatory mechanism is involved in LPS-induced EIU. In this study, we report that miR-93 expression in the eyes of EIU rats and LPS-stimulated macrophages is significantly decreased. We also show that miR-93 inhibits NF-κB activation and pro-inflammatory cytokines by targeting IRAK4 expression. We further demonstrate that miR-93 inhibits IRAK4 expression by binding directly to the 3'-UTR of IRAK4. Our findings suggest that miR-93 is a negative regulator of the immune response in EIU.

Keywords: IRAK4; LPS; MicroRNA-93.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Binding Sites
  • Cytokines / metabolism
  • Down-Regulation
  • Eye / immunology
  • Eye / metabolism
  • Eye / pathology
  • Gene Expression Regulation, Enzymologic / immunology
  • HEK293 Cells
  • Humans
  • Interleukin-1 Receptor-Associated Kinases / genetics*
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Male
  • Mice
  • MicroRNAs / physiology*
  • NF-kappa B / metabolism
  • RNA Interference*
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Uveitis / immunology
  • Uveitis / metabolism

Substances

  • 3' Untranslated Regions
  • Cytokines
  • Lipopolysaccharides
  • MicroRNAs
  • Mirn93 microRNA, mouse
  • NF-kappa B
  • Interleukin-1 Receptor-Associated Kinases
  • Irak4 protein, mouse