Interleukin-10 inhibits interleukin-1β production and inflammasome activation of microglia in epileptic seizures

Abstract

Background Microglia are important for secreting chemical mediators of inflammatory responses in the central nervous system. Interleukin (IL)-10 and IL-1β secreted by glial cells support neuronal functions, but the related mechanisms remain vague. Our goal was to demonstrate the efficacy of IL-10 in suppressing IL-1β and in inflammasome activation in mice with epileptic seizure based on an epileptic-seizure mouse model. Methods In this study, mice in which epileptic seizures were induced by administering picrotoxin (PTX) were used as a case group, and mice injected with saline were employed as the control group. The expression of nucleic acids, cytokines, or signaling pathways was detected by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), flow cytometry, and Western blotting. Results Our results demonstrated that IL-10 inhibits IL-1β production through two distinct mechanisms: (1) Treatment with lipopolysaccharides (LPS) results in IL-10 overexpression in microglia and reduced NLRP3 inflammasome activity, thus inhibiting caspase-1-related IL-1β maturation; (2) next, autocrine IL-10 was found to subsequently promote signal transducer and activator of transcription-3 (STAT-3), reducing amounts of pro-IL-1β. Conclusions Our results indicate that IL-10 is potentially effective in the treatment of inflammation encephalopathy, and suggest the potential usefulness of IL-10 for treating autoimmune or inflammatory ailments. Electronic supplementary material The online version of this article (10.1186/s12974-019-1452-1) contains supplementary material, which is available to authorized users.

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The Dichotomous Role of Inflammation in the CNS: A Mitochondrial Point of View

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