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

Prostaglandins have been shown to be involved in the suppression of contact hyper sensitivity (CHS) by so-far ill understood mechanisms. T-cell migration across the lining of cytokine-activated endothelial cells (EC) is thought to be a central step in the initiation of CHS. The aim of our investigation was therefore to examine whether prostaglandin E[sub1] (PGE[sub1]) influences cytokine-induced TK-1 mouse lymphoma adhesion to eEnd.2 mouse endothelioma cells. Here, we report that PGE[sub1] (10[sup―12]10[sup―8] M) dose-dependently induced TNFα-induced T-cell binding, while TNFα-unstimulated adhesion was not affected. To test whether PGE[sub1], acted primarily on T-cells or on EC, they were separately pretreated with PGE[sub1] prior to the adhesion assay. Selective PGE[sub1] pretreatment of eEnd.2, but not of TK-1 dose-dependently inhibited TN Fα, 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-ceIIs), we further investigated whether PGE[sub1] would modulate the expression of these molecules FACS-analysis revealed PGE[sub1] to inhibit TNFα-induced upregulation of ICAM-1, but not of VCAM-1 on EC. Furthermore, constitutive LFA-1 and VLA-4 expression on T-cells was not affected by PGE[sub1]. We conclude that PGE[sub1] 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. [ABSTRACT FROM AUTHOR]