title: Adenovirus-delivered angiopoietin-1 suppresses NF-κB and p38 MAPK and attenuates inflammatory responses in phosgene-induced acute lung injury.
abstract: Animals exposed to phosgene (Psg) result in acute lung injury (ALI). We have recently reported that angiopoietin-1 (Ang1) reduces inflammation and vascular hyperpermeability in ALI animals. In this study, we examined whether the beneficial effects of adenovirus-delivered Ang1 (Ad/Ang1) on inflammatory responses in Psg-induced ALI rats are due to the suppression of the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways, which play crucial roles in inflammatory responses in ALI. We demonstrated that Psg increased Ang2 and inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-4 (IL-4), IL-6, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid of ALI rats, determined by ELISA. Ang1 inhibits pro-inflammatory mediators (TNF-α, IL-6 and IL-8) and has no effect on anti-inflammatory mediators (IL-4 and IL-10). Furthermore, the inhibitory action of Ang1 was mediated by the suppression of the NF-κB and p38 MAPK pathways, leading to the attenuation of inflammatory responses of ALI. Thus, Ad/Ang1 may provide a useful tool for the effective treatment in Psg-induced ALI.
authors: Center of Emergency & Intensive Care Unit .
authors: Dai-Kun
authors: DK
authors: He
authors: Yi-Ru
authors: YR
authors: Shao
authors: Lin
authors: L
authors: Zhang
authors: Jie
authors: J
authors: Shen
authors: Zhi-Yue
authors: ZY
authors: Zhong
authors: Jing
authors: J
authors: Wang
authors: Guoxiong
authors: G
authors: Xu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000256:Adenoviridae; D042683:Angiopoietin-1 / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002619:Chemical Warfare Agents / Q000633:toxicity*; D016207:Cytokines / Q000276:immunology; D016503:Drug Delivery Systems; D005822:Genetic Vectors; D019570:Inhalation Exposure; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D010705:Phosgene / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D042683:Angiopoietin-1; D002619:Chemical Warfare Agents; D016207:Cytokines; D016328:NF-kappa B; D010705:Phosgene; D048051:p38 Mitogen-Activated Protein Kinases