IL-17 signaling induces iNOS+ microglia activation in retinal vascular diseases

Glia. 2021 Nov;69(11):2644-2657. doi: 10.1002/glia.24063. Epub 2021 Jul 21.

Abstract

Activation of microglia and inflammation-mediated vascular damages are suggested to play a decisive role in the pathogenesis of various retinopathies. The inducible nitric oxide synthase (iNOS) was required for activated microglia-mediated injuries. However, the induction mechanism of microglia activation during retinal vascular diseases is still elusive. Here we showed that IL-17 induced microglia activation with high expression of iNOS and promoted the development of retinal vascular diseases. IL-17-dependent activation of the STAT3-iNOS pathway was essentially required for microglia activation, which promoted endothelial cell growth and accelerated vascular leakage and leukostasis via IL-6 in vitro and in vivo. Taken together, our data provide novel mechanistic insights on microglia activation-mediated retinopathy, unveil the specific role of IL-17 on microglia, and define novel therapeutic targets for treating retinal vascular diseases.

Keywords: IL-17; iNOS; inflammation; microglia activation; retinal vascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Interleukin-17* / metabolism
  • Microglia / metabolism
  • Nitric Oxide Synthase Type II* / metabolism
  • Retinal Diseases* / metabolism
  • Vascular Diseases* / metabolism
  • Vascular Diseases* / pathology

Substances

  • Interleukin-17
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II