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  • Blockade of PDE4B limits lung vascular permeability and lung inflammation in LPS-induced acute lung injury.

Blockade of PDE4B limits lung vascular permeability and lung inflammation in LPS-induced acute lung injury.

Biochemical and biophysical research communications (2014-07-16)
Hongyan Ma, Jinghui Shi, Changsong Wang, Lei Guo, Yulei Gong, Jie Li, Yongtai Gong, Fengxiang Yun, Hongwei Zhao, Enyou Li
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting human PDE4B
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Pde4b
Diazepam, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Cilomilast, ≥95% (HPLC)
Supelco
Diazepam solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Diazepam