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Effects of prostaglandin lipid mediators on agonist-induced lung endothelial permeability and inflammation

Year: 2017
Type: article
Abstract: Prostaglandins (PG), the products of cyclooxygenase-mediated conversion of arachidonic acid, become upregulated in many situations including allergic response, inflammation, and injury, and exhibit a variety of biological activities. Previous studies described barrier-enhancing and anti-inflammatory effects of PGE2and PGI2on vascular endothelial cells (EC). Yet, the effects of other PG members on EC barrier and inflammatory activation have not been systematically analyzed. This study compared effects of PGE2, PGI2, PGF2α, PGA2, PGJ2, and PGD2on human pulmonary EC. EC permeability was assessed by measurements of transendothelial electrical resistance and cell monolayer permeability for FITC-labeled tracer. Anti-inflammatory effects of PGs were evaluated by analysis of expression of adhesion molecule ICAM1 and secretion of soluble ICAM1 and cytokines by EC. PGE2, PGI2, and PGA2exhibited the most potent barrier-enhancing effects and most efficient attenuation of thrombin-induced EC permeability and contractile response, whereas PGI2effectively suppressed thrombin-induced permeability but was less efficient in the attenuation of prolonged EC hyperpermeability caused by interleukin-6 or bacterial wall lipopolysaccharide, LPS. PGD2showed a modest protective effect on the EC inflammatory response, whereas PGF2αand PGJ2were without effect on agonist-induced EC barrier dysfunction. In vivo, PGE2, PGI2, and PGA2attenuated LPS-induced lung inflammation, whereas PGF2αand PGJ2were without effect. Interestingly, PGD2exhibited a protective effect in the in vivo model of LPS-induced lung injury. This study provides a comprehensive analysis of barrier-protective and anti-inflammatory effects of different prostaglandins on lung EC in vitro and in vivo and identifies PGE2, PGI2, and PGA2as prostaglandins with the most potent protective properties.
DOI: 10.1152/ajplung.00519.2016
Authors: Yunbo Ke, Olga V. Oskolkova, Nicolene Sarich, Yufeng Tian, Albert Sitikov, Mohan E. Tulapurkar, Sophia Son, Anna A. Birukova, Konstantin G. Birukov
Language: English
Subfield: Pharmacology
Field: Medicine
Open Access status: green
Awards: G1695898165, G214086788, G3389786192, Molecular control of lung endothelial barrier function in ALI, G364505434, G5117733777, G5385378051, G5854265684, Microtubule-associated regulation of acute lung injury, Control of lung permeability by oxidized phospholipids, G736871325
OpenAlex ID: W2726010605
FWCI: 2.289
Cites: 35
Cited by: 28
Related to: 10