Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 313, Issue 4, Pages L710-L721Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00519.2016
Keywords
pulmonary endothelial cells; permeability; inflammation; prostaglandins; acute lung injury
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Funding
- National Heart, Lung, and Blood Institute Grants [HL-076259, HL-087823, HL-107920]
- National Institute of General Medical Sciences Grant [GM-114171]
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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 PGE(2) and PGI(2) 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 PGE(2), PGI(2), PGF(2 alpha), PGA(2), PGJ(2), and PGD(2) on human pulmonary EC. EC permeability was assessed by measurements of transendothelial electrical resistance and cell monolayer permeability for FITC-labeled tracer. Antiinflammatory effects of PGs were evaluated by analysis of expression of adhesion molecule ICAM1 and secretion of soluble ICAM1 and cytokines by EC. PGE(2), PGI(2), and PGA(2) exhibited the most potent barrier- enhancing effects and most efficient attenuation of thrombininduced EC permeability and contractile response, whereas PGI(2) 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. PGD(2) showed a modest protective effect on the EC inflammatory response, whereas PGF(2 alpha) and PGJ(2) were without effect on agonist-induced EC barrier dysfunction. In vivo, PGE(2), PGI(2), and PGA(2) attenuated LPS-induced lung inflammation, whereas PGF(2 alpha) and PGJ(2) were without effect. Interestingly, PGD(2) 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 PGE(2), PGI(2), and PGA(2) as prostaglandins with the most potent protective properties.
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