BRD4 is involved in viral exacerbation of chronic obstructive pulmonary disease

Respiratory Research

Research

Siyi Zhou¹  Jianmiao Wang¹  Yifei Duan¹ 

[1] Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, 430030, Wuhan, China;

关键词: Bromodomain protein 4 (BRD4);    Chronic obstructive pulmonary disease;    Exacerbation;    Inflammation;    Viral infection;   

DOI  :  10.1186/s12931-023-02348-y

 received in 2022-06-25, accepted in 2023-01-27,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundOur previous studies have suggested that bromodomain protein 4 (BRD4) is increased in the lung of stable chronic obstructive pulmonary disease (COPD) patients, which has been shown to be involved in inflammatory responses. We investigated its role in the viral exacerbation of COPD.MethodsBRD4, interleukin (IL)-6 and IL-8 were measured in the blood and sputum of stable COPD patients and patients with viral exacerbation. Mice were exposed to cigarette smoke (CS) and/or infected with influenza virus as an in vivo model. BRD4, IL-6 and keratinocyte-derived chemokine (KC) were measured in the lung. BEAS-2B cells were treated with CS extract and/or influenza virus as an in vitro model. BRD4, IL-6 and IL-8 were measured in the cells and/or culture supernatant.ResultsBRD4 was increased in COPD patients with viral exacerbation compared with those in stable condition and its expression was correlated with IL-6 and IL-8 expression. Inflammatory cells, IL-6, KC and BRD4 were synergistically induced in the lung of mice by viral infection and CS exposure, and the former three were decreased by JQ1 (BRD4 inhibitor) treatment. IL-6, IL-8 and BRD4 were significantly induced by CS extract and influenza virus in bronchial epithelial cells, and this upregulation was suppressed by knockdown of BRD4 expression.ConclusionsOur findings indicate that CS and viruses may synergistically induce IL-6 and IL-8 expression through their synergistic induction of BRD4 expression, which might contribute to the enhanced inflammatory response in the viral exacerbation of COPD.

【 授权许可】

CC BY   
© The Author(s) 2023

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