PMID- 36605203 OWN - NLM STAT- MEDLINE DCOM- 20230109 LR - 20231213 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Complement component 3 protects human bronchial epithelial cells from cigarette smoke-induced oxidative stress and prevents incessant apoptosis. PG - 1035930 LID - 10.3389/fimmu.2022.1035930 [doi] LID - 1035930 AB - The complement component 3 (C3) is a pivotal element of the complement system and plays an important role in innate immunity. A previous study showed that intracellular C3 was upregulated in airway epithelial cells (AECs) from individuals with end-stage chronic obstructive pulmonary disease (COPD). Accumulating evidence has shown that cigarette smoke extract (CSE) induces oxidative stress and apoptosis in AECs. Therefore, we investigated whether C3 modulated cigarette smoke-induced oxidative stress and apoptosis in AECs and participated in the pathogenesis of COPD. We found increased C3 expression, together with increased oxidative stress and apoptosis, in a cigarette smoke-induced mouse model of COPD and in AECs from patients with COPD. Different concentrations of CSEinduced C3 expression in 16HBE cells in vitro. Interestingly, C3 knockdown (KD) exacerbated oxidative stress and apoptosis in 16HBE cells exposed to CSE. Furthermore, C3 exerted its pro-survival effects through JNK inhibition, while exogenous C3 partially rescued CSE-induced cell death and oxidative stress in C3 KD cells. These data indicate that locally produced C3 is an important pro-survival molecule in AECs under cigarette smoke exposure, revealing a potentially novel mechanism in the pathogenesis of COPD. CI - Copyright (c) 2022 Pei, Zhang, Qu, Rao, Li, Gai, Chen, Liang and Sun. FAU - Pei, Yuqiang AU - Pei Y AD - Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China. FAU - Zhang, Jing AU - Zhang J AD - Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China. FAU - Qu, Jingge AU - Qu J AD - Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China. FAU - Rao, Yafei AU - Rao Y AD - Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China. FAU - Li, Danyang AU - Li D AD - Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China. FAU - Gai, Xiaoyan AU - Gai X AD - Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China. FAU - Chen, Yahong AU - Chen Y AD - Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China. FAU - Liang, Ying AU - Liang Y AD - Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China. FAU - Sun, Yongchang AU - Sun Y AD - Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221220 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Complement C3) SB - IM MH - Animals MH - Mice MH - Humans MH - *Cigarette Smoking/adverse effects MH - Complement C3/metabolism MH - Oxidative Stress MH - *Pulmonary Disease, Chronic Obstructive/pathology MH - Epithelial Cells/metabolism MH - Apoptosis MH - Nicotiana/metabolism PMC - PMC9807617 OTO - NOTNLM OT - apoptosis OT - chronic obstructive pulmonary disease OT - cigarette smoke OT - complement C3 OT - oxidative stress COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/01/07 06:00 MHDA- 2023/01/10 06:00 PMCR- 2022/01/01 CRDT- 2023/01/06 02:28 PHST- 2022/09/29 00:00 [received] PHST- 2022/12/06 00:00 [accepted] PHST- 2023/01/06 02:28 [entrez] PHST- 2023/01/07 06:00 [pubmed] PHST- 2023/01/10 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.1035930 [doi] PST - epublish SO - Front Immunol. 2022 Dec 20;13:1035930. doi: 10.3389/fimmu.2022.1035930. eCollection 2022.