title: Blockade of PDE4B limits lung vascular permeability and lung inflammation in LPS-induced acute lung injury.
abstract: Acute lung injury (ALI), acute respiratory distress syndrome (ARDS), is actually involved in an ongoing and uncontrolled inflammatory response in lung tissues. Although extensive studies suggested that phospodiesterase type 4B (PDE4B) may be related to inflammation, the underlying cell biological mechanism of ALI remains unclear. To further investigate the mechanism how PDE4B take part in inflammatory response and the maintenance of vascular integrity, we established the experimental model of ALI in vitro and in vivo. In vitro, we found that Cilomilast, Diazepam and PDE4B knockout could potently inhibit the LPS-induced NF-κB activation and inflammatory response in multiple cell types, including lung epithelial cells (A549), pulmonary microvascular endothelial cells (PMVECs) and vascular smooth muscle cells (VSMCs). Besides, PDE4B deletion attenuated the LPS-induced ROS generation. In vivo, PDE4B deletion could attenuate the lung water content, histological signs of pulmonary injury and elevate the ratio of partial pressure of arterial O2 to fraction of inspired O2 (PaO2/FIO2 ratio). Additionally, PDE4B deletion reduced LPS-induced vascular permeability. Collectively, our results strongly indicates that PDE4B is a valid target for anti-ALI.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China.
authors.forename: Changsong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China.
authors.forename: Yulei
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510000, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China.
authors.forename: Yongtai
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Cardiovascular Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China.
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Yun
authors.affiliation: Department of Cardiovascular Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China. Electronic address: lienyouhydyymzk@yeah.net.
authors.forename: Enyou
authors.initials: E
authors.lastname: Li
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D000818:Animals; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000187:drug effects*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D011014:Pneumonia / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D058988:Phosphodiesterase 4 Inhibitors; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C546993:PDE4B protein, rat
keywords: Acute lung injury; LPS; PDE4B; Vascular barrier dysfunction