Involvement of nitric oxide in the induction of interleukin-1 beta in microglia

Brain Research
Kenji SudoKazuyuki Nakajima

Abstract

In response to in vitro stimulation with lipopolysaccharide (LPS), microglia induce the production of the inflammatory cytokine interleukin-1 beta (IL-1β) together with nitric oxide (NO) and superoxide anion (O2(-)). Here we investigated the role of NO and O2(-) in the signaling mechanism by which IL-1β is induced in microglia. The LPS-inducible IL-1β was significantly suppressed by pretreatment with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide, but not by pretreatment with the O2(-) scavenger N-acetyl cysteine, suggesting the close association of NO with IL-1β induction. The pretreatment of microglia with the inducible NO synthase inhibitor 1400W prior to LPS stimulation significantly reduced the production of IL-1β, and the addition of the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) into microglia led to the induction of IL-1β. These results suggested that NO induces IL-1β through a specific signaling cascade. LPS-dependent IL-1β induction was significantly suppressed by inhibitors of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and nuclear factor kappaB (NFκB), indicating that ERK/JNK and NFκB serve in the cascade of IL-1β induction. As expected, ERK...Continue Reading

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Citations

Sep 26, 2019·Neural Regeneration Research·Rachel KeryGregory W Kirschen
Aug 28, 2020·Frontiers in Cellular Neuroscience·Ada BernausAna Sevilla
Dec 15, 2018·Glia·Qiao-Qiao Yang, Jia-Wei Zhou
Feb 18, 2021·Psychopharmacology·Ying YangYuanyuan Cheng

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