title: Cigarette Smoke-Induced Pulmonary Inflammation and Autophagy Are Attenuated in Ephx2-Deficient Mice.
abstract: Cigarette smoke (CS) increases the risk of chronic obstructive pulmonary disease (COPD) by causing inflammation, emphysema, and reduced lung function. Additionally, CS can induce autophagy which contributes to COPD. Arachidonic acid-derived epoxyeicosatrienoic acids (EETs) have promising anti-inflammatory properties that may protect the heart and liver by regulating autophagy. For this reason, the effect of decreased soluble epoxide hydrolase (sEH, Ephx2)-mediated EET hydrolysis on inflammation, emphysema, lung function, and autophagy was here studied in CS-induced COPD in vivo. Adult male wild-type (WT) C57BL/6J and Ephx2-/-mice were exposed to air or CS for 12 weeks, and lung inflammatory responses, air space enlargement (emphysema), lung function, and autophagy were assessed. Lungs of Ephx2-/-mice had a less pronounced inflammatory response and less autophagy with mild distal airspace enlargement accompanied by restored lung function and steady weight gain. These findings support the idea that Ephx2 may hold promise as a therapeutic target for COPD induced by CS, and it may be protective property by inhibiting autophagy.
authors.affiliation: The Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong An Road, Xichen District, Beijing, 100050, China.
authors.forename: Yunxiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong An Road, Xichen District, Beijing, 100050, China.
authors.forename: Ganggang
authors.initials: G
authors.lastname: Yu
authors.affiliation: Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Yuan
authors.affiliation: The Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong An Road, Xichen District, Beijing, 100050, China.
authors.forename: Chunting
authors.initials: C
authors.lastname: Tan
authors.affiliation: Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Puqiao
authors.initials: P
authors.lastname: Lian
authors.affiliation: Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Fu
authors.affiliation: Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Hou
authors.affiliation: The Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong An Road, Xichen District, Beijing, 100050, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: The Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong An Road, Xichen District, Beijing, 100050, China. haoyanw@ccmu.edu.cn.
authors.forename: Haoyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy; D004646:Emphysema / Q000209:etiology; D004851:Epoxide Hydrolases / Q000172:deficiency*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000209:etiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects
chemical_list: D012906:Smoke; D004851:Epoxide Hydrolases; C518648:Ephx2 protein, mouse
keywords: Ephx2; autophagy; cigarette smoke; epoxyeicosatrienoic acids; inflammation