title: Activating transcription factor 3 represses cigarette smoke-induced IL6 and IL8 expression via suppressing NF-κB activation.
abstract: Airway and lung inflammation is a fundamental hallmark of chronic obstructive pulmonary disease (COPD). Activating transcription factor 3 (ATF3) has been reported to negatively regulate many pro-inflammatory cytokines and chemokines. However, little is known about the impact of ATF3 on the inflammatory response of COPD. Since cigarette smoke (CS) is considered to be the most important risk factor in the etiology of COPD, we attempted to investigate the effects and molecular mechanisms of ATF3 in CS-induced inflammation. We observed an increase in the expression of ATF3 in the lung tissues of CS-exposed mice and CS extract (CSE)-treated human bronchial epithelial (HBE) cells. In vitro results indicated that ATF3 inhibition significantly increased the expression of proinflammatory cytokines interleukin 6 (IL6) and interleukin 8 (IL8) in CSE-stimulated HBE cells. Furthermore, in vivo data verified that CS induced inflammatory cell recruitment around the bronchus. In addition, neutrophil infiltration in bronchoalveolar lavage fluid (BALF) of CS-exposed Atf3-/-mice was markedly higher than in stimulated WT mice. Finally, ATF3 deficiency increased the in vitro and in vivo expression and phosphorylation of nuclear factor-κB (NF-κB), a positive mediator of inflammation. Thus, this study shows that ATF3 plays an important role in the negative regulation of CS-induced pro-inflammatory gene expression through downregulating NF-κB phosphorylation.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, Ningbo First Hospital, Ningbo, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yin-Fang
authors.initials: YF
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Tian-Wen
authors.initials: TW
authors.lastname: Lai
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Song-Min
authors.initials: SM
authors.lastname: Ying
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; State Key Lab of Respiratory Disease, Key site of National Clinical Research Center for Respiratory Disease, Guangzhou, China. Electronic address: huahaoshen@163.com.
authors.forename: Hua-Hao
authors.initials: HH
authors.lastname: Shen
authors.affiliation: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: liwenzjhz0408@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D015536:Down-Regulation; D063185:Epigenetic Repression; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000302:isolation & purification; D012907:Smoking / Q000009:adverse effects*; D015854:Up-Regulation
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D034741:RNA, Small Interfering
keywords: Activating transcription factor 3; Cigarette smoke; Interleukin 6; Interleukin 8; Nuclear factor-κB