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

• Published in: Journal of neuroinflammation Vol. 16; no. 1; pp. 66 - 13
• Main Authors: Sun, Yi, Ma, Jiangjun, Li, Dongfang, Li, Pinggan, Zhou, Xiaolin, Li, Yu, He, Zhanwen, Qin, Lijun, Liang, Liyang, Luo, Xiangyang
• Format: Journal Article
• Language: English
• Published: London BioMed Central 28.03.2019; BMC
• Subjects: Animals; Autocrine signalling; Biomedical and Life Sciences; Biomedicine; Brain - pathology; Brain research; Caspase; Caspase-1; Cell adhesion & migration; Cells, Cultured; Central nervous system; Convulsants - toxicity; Convulsions & seizures; Cytokines; Cytokines - genetics; Cytokines - metabolism; Disease; Disease Models, Animal; Encephalopathy; Enzyme-linked immunosorbent assay; Epilepsy; Flow cytometry; Gene Expression Regulation - drug effects; Glial cells; IL-10; IL-1β; Immunology; Inflammasomes; Inflammation; Interleukin 10; Interleukin-10 - pharmacology; Interleukin-1beta - metabolism; Lipopolysaccharides; Lipopolysaccharides - toxicity; Male; Mice; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Microglia - metabolism; Nervous system; Neurobiology; Neurology; Neuronal-glial interactions; Neurosciences; Nucleic Acids - genetics; Nucleic Acids - metabolism; Picrotoxin; Picrotoxin - toxicity; Polyclonal antibodies; Polymerase chain reaction; Reverse transcription; RNA, Small Interfering - pharmacology; Seizures; Seizures - chemically induced; Seizures - metabolism; Seizures - pathology; Signal Transduction - drug effects; Signal Transduction - genetics; Stat3 protein; STAT3 Transcription Factor - metabolism; Tumor necrosis factor-TNF; Western blotting; United States > US; IL-1β; Epilepsy; IL-10; Microglia
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-019-1452-1

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.