4.6 Article

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

期刊

GLIA
卷 69, 期 11, 页码 2644-2657

出版社

WILEY
DOI: 10.1002/glia.24063

关键词

IL-17; inflammation; iNOS; microglia activation; retinal vascular diseases

资金

  1. National Key R&D Program of China [2018YFA0108300]
  2. National Natural Science Foundation of China [81630022, 81900886]
  3. Natural Science Foundation of Guangdong Province [2019B151502006]
  4. Science and Technology Program of Guangzhou, China [201906010076]

向作者/读者索取更多资源

Inflammatory-mediated activation of microglia and iNOS play a crucial role in retinopathies, with IL-17 inducing microglia activation and promoting the development of retinal vascular diseases. Activation of the STAT3-iNOS pathway by IL-17 is essential for microglia activation, leading to endothelial cell growth and vascular leakage via IL-6.
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.

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