Monocyte chemotactic protein-inducing protein 1 negatively regulating asthmatic airway inflammation and mucus hypersecretion involving γ-aminobutyric acid type A receptor signaling pathway in vivo and in vitro
Authors: Jia-Jia Wang
Guang-Ming Dai
Ruo-Lin Mao
Ya-Juan Ran
Huo-Jin Deng
Tao Zhu
Zhi-Hong Chen
Journal: Chinese Medical Journal (2021)
Discipline: CLINICAL MEDICINE
Keywords: GABAAR; MCPIP1; airway inflammation; mucus hypersecretion; asthma
Affiliations: Department of Respiratory Medicine, First People's Hospital of Suining City, Suining, Sichuan 629000, China., Department of Rheumatology Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China., Department of Respiratory Medicine, Zhongshan Hospital of Fudan University, Shanghai 200032, China., Department of Pharmacy, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China., Department of Respiratory Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510280, China., Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

Abstract:  Background: Mounting evidence, consistent with our previous study, showed that γ-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 &lt; 0.001) and plasmid-MCPIP1 (P &lt; 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 &lt; 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 &lt; 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. 

Retracted: No

PubPeer comments:
 There is an image duplication in Figure 1, where two histology images supposedly from mice belonging to different experimental groups are in fact the same histology slide. ![file] , 
 Dear Coniochaeta Malacotricha Thank you for pointing out this error. We have examined the raise issues thoroughly. We carefully reviewed and checked the original data and figures. All the original data are true and reliable. However, we also noticed that this error was made during figure preparations. And the revised figure was provided below. We apologize for this error. This error doesnu2019t affect the scientific conclusions of this study. Thanks again for your comments! Yours sincerely, Tao Zhu ![file] ,