Effects of tumor necrosis factor on prostacyclin production and the barrier function of human endothelial cell monolayers

E G Langeler, W Fiers, V W van Hinsbergh
1991 Arteriosclerosis and Thrombosis A Journal of Vascular Biology  
The endothelium controls the influx of macromolecules into the tissues, a process that may be disturbed at sites of inflammation and in atherosclerotic plaques. In this article, we report our evaluations of the effects of the inflammatory mediator, tumor necrosis factor-a (TNF-or), on the production of prostacyclin and the barrier function of human endothelial cell monolayers in an in vitro model. TNF-a (500 units/ml) had no direct effect on the passage of sucrose, peroxidase, and low density
more » ... , and low density lipoprotein through monolayers of human aortic endothelial cells. On the other hand, during the first hours after addition 500 units/ml TNF-or induced a reduction of the permeability of umbilical artery endothelial cell monolayers. Within 10 minutes TNF-ar induced an increase in prostacyclin production by primary cultures of umbilical artery endothelial cells. However, the reduction in permeability was not caused by a change in prostacyclin production or by a change in cyclic AMP concentration because 1) the effect of TNF-« on permeability was not prevented by aspirin, 2) no change in the cellular cyclic AMP concentration could be observed after addition of TNF-oi and 3) TNF-orwas still able to reduce the passage rate in the presence of 25 fxM forskolin. The reduction in permeability was accompanied by a decrease of F-actin in stress fibers. With prolonged incubation with TNF-o^ the permeability of umbilical artery endothelial cell monolayers increased, and F-actin was found again in stress fibers. However, these effects of TNF-ar were only significant at high concentrations of TNF-«. Because high TNF-a concentrations only persist in vivo for short periods and no increase in the permeability of human aortic endothelial permeability was observed after incubation with TNF-a, it is unlikely that TNF-a plays a role in the increased permeability that has been found in human arteriosclerotic lesions. (Arteriosclerosis and Thrombosis 1991;11:872-881) From the Gaubius Institute TNO (E.G.L., V.W.M.v
doi:10.1161/01.atv.11.4.872 fatcat:ani5r5un7bfwjnjav2hteadlym