Monocyte chemotactic protein-inducing protein 1 negatively regulating asthmatic airway inflammation and mucus hypersecretion involvingγ-aminobutyric acid type A receptor signaling pathway in vivo and in vitro  

作　　者：Guang-Ming Dai Jia-Jia Wang Zhi-Hong Chen Ya-Juan Ran Huo-Jin Deng Ruo-Lin Mao Tao Zhu 

机构地区：[1]Department of Respiratory Medicine,First People's Hospital of Suining City,Suining,Sichuan 629000,China [2]Department of Rheumatology Medicine,Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China [3]Department of Respiratory Medicine,Zhongshan Hospital of Fudan University,Shanghai 200032,China [4]Department of Pharmacy,Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China [5]Department of Respiratory Medicine,Zhujiang Hospital of Southern Medical University,Guangzhou,Guangdong 510280,China [6]Department of Respiratory Medicine,Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China

出　　处：《Chinese Medical Journal》2021年第1期88-97,共10页中华医学杂志（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China for Young Scholar(No.81801484);China Postdoctoral Science Foundation(No.2014M552369);Natural Science Foundation of Guangdong Province(No.2017A030310286);Scientific Research Project of Guangzhou(No.201707010282)。

摘　　要：Background:Mounting evidence,consistent with our previous study,showed thatγ-aminobutyric acid type A receptor(GABAAR)played an indispensable role in airway inflammation and mucus hypersecretion in asthma.Monocyte chemotactic protein-inducing protein 1(MCPIP1)was a key negative regulator of inflammation.Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases.However,the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied.This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells,and its potential mechanism.Methods:In vivo,mice were sensitized and challenged by ovalbumin(OVA)to induce asthma.Airway inflammation and mucus secretion were analyzed.In vitro,BEAS-2B cells were chosen.Interleukin(IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells.MCPIP1 Lentiviral vector(LA-MCPIP1)and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells,respectively.MCP-1,thymic stromal lymphopoietin(TSLP),mucin 5AC(MUC5AC),MCPIP1,and GABAARβ2 expressions were measured in both lung and BEAS-2B cells.Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells.Results:MCPIP1 was up-regulated by LA-MCPIP1(P<0.001)and plasmid-MCPIP1(P<0.001)in lung and cells,respectively.OVA-induced airway inflammation and mucus hypersecretion,OVA-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice(all P<0.001).IL-13-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells(all P<0.001).Conclusion:The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells,involving GABAAR signaling pathway.

关 键 词：Airway inflammation Airway mucus hypersecretion Gamma-aminobutyric acid type A receptor GABAAR IL-13 MCPIP1 Monocyte chemotactic protein-inducing protein 1 OVALBUMIN 

分 类 号：R562.25[医药卫生—呼吸系统]