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Prostaglandin E 1 inhibits TNFα‐induced T‐cell adhesion to endothelial cells by selective down‐modulation of ICAM‐1 expression on endothelial cells *
Author(s) -
Weiss J. M.,
Pilarski K. A.,
Wcyl A.,
Peschen M.,
Schöpf E.,
Vestweber D.,
Vanscheidt W,
Simon J. C.
Publication year - 1995
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.1995.tb00209.x
Subject(s) - icam 1 , microbiology and biotechnology , adhesion , endothelial stem cell , cell adhesion , chemistry , intercellular adhesion molecule 1 , intracellular , cell , biology , biochemistry , in vitro , organic chemistry
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 E 1 (PGE 1 ) influences cytokine‐induced TK‐1 mouse T‐cell lymphoma adhesion to eEnd.2 mouse endothelioma cells. Here, we report that PGE 1 (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 PGE 1 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 PGE 1 would modulate the expression of these molecules. FACS‐analysis revealed PGE 1 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 PGE 1 . We conclude that PGE 1 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.