Interleukin-19 acts as a negative autocrine regulator of activated microglia

PloS One
Hiroshi HoriuchiAkio Suzumura

Abstract

Activated microglia can exert either neurotoxic or neuroprotective effects, and they play pivotal roles in the pathogenesis and progression of various neurological diseases. In this study, we used cDNA microarrays to show that interleukin-19 (IL-19), an IL-10 family cytokine, is markedly upregulated in activated microglia. Furthermore, we found that microglia are the only cells in the nervous system that express the IL-19 receptor, a heterodimer of the IL-20Rα and IL-20Rβ subunits. IL-19 deficiency increased the production of such pro-inflammatory cytokines as IL-6 and tumor necrosis factor-α in activated microglia, and IL-19 treatment suppressed this effect. Moreover, in a mouse model of Alzheimer's disease, we observed upregulation of IL-19 in affected areas in association with disease progression. Our findings demonstrate that IL-19 is an anti-inflammatory cytokine, produced by activated microglia, that acts negatively on microglia in an autocrine manner. Thus, microglia may self-limit their inflammatory response by producing the negative regulator IL-19.

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Citations

Feb 24, 2016·Mediators of Inflammation·Mary K Wirtz, Kate E Keller
May 14, 2016·Scientific Reports·Akiyuki UzawaSatoshi Kuwabara
Jul 16, 2020·American Journal of Physiology. Cell Physiology·Tani LeighMichael V Autieri
Dec 14, 2018·Frontiers in Cellular Neuroscience·Amanda R Burmeister, Ian Marriott
Aug 14, 2019·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Yasuyuki Fujimoto, Yasu-Taka Azuma
Jul 24, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Deirdre A KillebrewRick B Meeker

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Methods Mentioned

BETA
PCR
ELISA

Software Mentioned

Agilent GeneSpring
GraphPad
GraphPad Prism

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