title: Resveratrol reduces acute lung injury in a LPS‑induced sepsis mouse model via activation of Sirt1.
abstract: The development of acute lung injury (ALI) during sepsis almost doubles the mortality rate of patients. The efficacy of current treatment strategies is low as treatment is usually initiated following the onset of symptoms. Inflammation is one of the main mechanisms of autoimmune disorders and is a common feature of sepsis. The suppression of inflammation is therefore an important mechanism for the treatment of sepsis. Sirtuin 1 (Sirt1) has been demonstrated to play a role in the regulation of inflammation. Resveratrol, a potent Sirt1 activator, exhibits anti‑inflammatory properties. However, the role of resveratrol for the treatment of ALI during sepsis is not fully understood. In the present study, the anti‑inflammatory role of Sirt1 in the lipopolysaccharide (LPS)‑induced TC‑1 cell line and its therapeutic role in ALI was investigated in a mouse model of sepsis. The upregulation of matrix metalloproteinase-9, interleukin (IL)‑1β, IL‑6 and inducible nitric oxide synthase was induced by LPS in the mouse model of sepsis and the TC‑1 cell line, and resveratrol suppressed the overexpression of these proinflammatory molecules in a dose‑dependent manner. Resveratrol decreased pulmonary edema in the mouse model of sepsis induced by LPS. In addition, resveratrol improved lung function and reduced pathological alterations in the mouse model of sepsis. Knockdown of Sirt1 by RNA interference resulted in an increased susceptibility of TC‑1 cells to LPS stimulation and diminished the anti‑inflammatory effect of resveratrol. These results demonstrated that resveratrol inhibits LPS‑induced ALI and inflammation via Sirt1, and indicated that Sirt1 is an efficient target for the regulation of LPS‑induced ALI and inflammation. The present study provides insights into the treatment of ALI during sepsis.
authors.affiliation: Stroke Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Tongxun
authors.initials: T
authors.lastname: Li
authors.forename: Jinglan
authors.initials: J
authors.lastname: Zhang
authors.forename: Jiliang
authors.initials: J
authors.lastname: Feng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Lisong
authors.initials: L
authors.lastname: Wu
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Jianping
authors.initials: J
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Mengran
authors.initials: M
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Cao
authors.forename: Guoan
authors.initials: G
authors.lastname: Xiang
authors.forename: Jinqian
authors.initials: J
authors.lastname: Zhang
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wu
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000077185:Resveratrol; D018805:Sepsis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D013267:Stilbenes; D052247:Nitric Oxide Synthase Type II; D020780:Matrix Metalloproteinase 9; D056564:Sirtuin 1; D000077185:Resveratrol