title: Protective effects of ethyl pyruvate on lipopolysaccharide‑induced acute lung injury through inhibition of autophagy in neutrophils.
abstract: Among a number of clinical factors, bacterial infection is one of the most common causes of acute lung injury (ALI), a serious complication that carries a high risk of mortality (~40%). During the process of ALI, intense local and systemic inflammation is elicited, which exacerbates the injury. Neutrophil infiltration into airspace is observed in early stage of ALI, and is required for the full development of ALI through an array of mechanisms, including the release of granule contents and the production of pro‑inflammatory cytokines, due to the overactivation of complement and cytokines. The present study noted that ethyl pyruvate alleviated ALI in lipopolysaccharide (LPS)‑induced ALI mice. Increased autophagy in neutrophils from ALI mice was observed, while ethyl pyruvate diminished autophagy in neutrophils and constrained granule release, and therefore myeloperoxidase (MPO) in bronchoalveolar lavage fluid and the production of proinflammatory cytokines. Using neutrophil cells, it was identified that autophagy was required for neutrophil activation and granule release, and that ethyl pyruvate caused neutrophil autophagy, leading to the restriction of granule release, and thus contributing to the mitigation of ALI. If autophagy was obviated through knockdown of key regulator of autophagy Atg5, the effects of ethyl pyruvate on granule release by neutrophils disappeared. Taken together, the results demonstrated that ethyl pyruvate alleviates ALI through inhibition of autophagy‑induced granule release by neutrophils, and this mechanism suggested a novel potential therapeutic target in autophagy regulation for ALI.
authors.affiliation: Department of Emergency Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Qingteng
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Respiratory Medicine, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Emergency Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Emergency Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Qirong
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Emergency Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Fei
authors.affiliation: Department of Emergency Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Shuming
authors.initials: S
authors.lastname: Pan
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D011773:Pyruvates / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D020011:Protective Agents; D011773:Pyruvates; C046522:ethyl pyruvate