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

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 PGE₂ and PGI₂ on 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, PGF_2α, PGA₂, PGJ₂, and PGD₂ on 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 PGA₂ exhibited the most potent barrier-enhancing effects and most efficient attenuation of thrombin-induced EC permeability and contractile response, whereas PGI₂ effectively suppressed thrombin-induced permeability but was less efficient in the attenuation of prolonged EC hyperpermeability caused by interleukin-6 or bacterial wall lipopolysaccharide, LPS. PGD₂ showed a modest protective effect on the EC inflammatory response, whereas PGF_2α and PGJ₂ were without effect on agonist-induced EC barrier dysfunction. In vivo, PGE₂, PGI₂, and PGA₂ attenuated LPS-induced lung inflammation, whereas PGF_2α and PGJ₂ were without effect. Interestingly, PGD₂ exhibited 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 PGA₂ as prostaglandins with the most potent protective properties.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ykVohp
via IFTTT