IL-4 inhibits formation of nod-like receptor protein 3 inflammasome mediated by high mobility group box-1 in microglia
10.3760/cma.j.issn.1671-8925.2018.04.007
- VernacularTitle:白介素-4抑制HMGB1介导的小胶质细胞NLRP3炎症复合体形成的机制研究
- Author:
Xiaolong YAO
1
;
Jiang QIAN
;
Wei DING
;
Pengjie YUE
;
Min ZHAO
;
Shengwen LIU
;
Huaqiu ZHANG
Author Information
1. 430030 武汉,华中科技大学同济医学院附属同济医院神经外科;430030武汉,泰康同济(武汉)医院神经外科
- Keywords:
NLRP3 inflammasome;
High mobility group box-1;
IL-4;
Microglia
- From:
Chinese Journal of Neuromedicine
2018;17(4):364-370
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the mechanisms by which IL-4 inhibits formation of nod-like receptor protein 3 (NLRP3) inflammasome mediated by high mobility group box-1 (HMGB1) in microglia.Methods After the primary microglia were cultured at the gradient concentrations of HMGB1 (100,200 and 400 ng/mL) for 3 hours and extracted,the effects of HMGB1 on the NLRP3 inflammasome and on the expression of downstream transcription factor NF-κB were detected by immunofluorescence and Western Blotting.Meanwhile,BAY 11-7082,an NF-κB inhibitor,and IL-4 were added in HMGB1 to observe the changes in the NLRP3 inflammasome and NF-κB expression.Results HMGB1 significantly promoted the formation and expression of NLRP3 inflammasome components like NLRP3,ASC and Caspase-1 in microglia in a concentration-dependent manner (P＜0.05).This effect was inhibited by BAY 11-7082.The levels of relative protein expression of NLRP3,ASC and Caspase-1 in the group of 400 ng/mL HMGB1+BAY were significantly lower than in the group of 400 ng/mL HMGB1 (P＜0.05).At the same time,IL-4 significantly decreased the formation of NLRP3 inflammasome induced by HMGB1.The levels of relative protein expression of NLRP3,ASC and Caspase-1 in the group of 400 ng/mL HMGB1+IL-4 were significantly lower than in the group of 400 ng/mL HMGB1 (P＜0.05).Further finding demonstrated that IL-4 inhibited the activity of NF-κB in microglia.Conclusions HMGB1 may promote formation ofNLRP3 inflammasome via activating the NF-κB in microglia;IL-4 may inhibit formation ofNLRP3 inflammasome mediated by HMGB1 through negative regulation of NF-κB activity.
