Prostaglandin E1 inhibits TNFα‐induced T‐cell adhesion to endothelial cells by selective down‐modulation of ICAM‐1 expression on endothelial cells*

Publisher Website
Google Scholar
Abstract
Prostaglandins have been shown to be involved in the suppression of contact hypersensitivity (CHS) by so‐far ill understood mechanisms. T‐cell migration across the lining of cytokine‐activated endo‐thelial cells (EC) is thought to be a central step in the initiation of CHS. The aim of our investigation was therefore to examine whether prosta‐glandin E1 (PGE1) influences cytokine‐induced TK‐1 mouse T‐cell lymphoma adhesion to eEnd.2 mouse endothelioma cells. Here, we report that PGE1 (10−12− 10−8 M) dose‐dependently reduced TNFα‐induccd T‐cell binding, while TNFα‐unstimulated adhesion was not affected. To test whether PGE, acted primarily on T‐cells or on EC, they were separately pretreated with PGE, prior to the adhesion assay. Selective PGE1 pretreatment of eEnd.2, but not of TK‐1 dose‐dependenlly inhibited TNFα, stimulated T‐cell adhesion. Since binding of TK‐1 to TNFα‐treated eEnd.2 is mediated by the interaction of ICAM‐1 and VCAM‐1 (on EC) with their receptors LFA‐1 and VLA‐4 (on T‐cells), we further investigated whether PGE1 would modulate the expression of these molecules. FACS‐analysis revealed PGE1 to inhibit TNFα‐induced upregulation of ICAM‐1, but not of VCAM‐I on EC. Furthermore, constitutive LFA‐1 and VLA‐4 expression on T‐cells was not affected by PGE1. We conclude that PGE1 supresses T‐cell adhesion to EC by selectively inhibiting TNFα‐induced upregulation of ICAM‐1 on EC. This may be one mechanism by which prostaglandins suppress immune responses requiring T‐cell EC interactions such as contact hypersensitivity in skin.

This publication has 19 references indexed in Scilit: