Prostaglandin E1 inhibits TNF alpha-induced T-cell adhesion to endothelial cells by selective down-modulation of ICAM-1 expression on endothelial cells.
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 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 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 TNF alpha-induced T-cell binding, while TNF alpha-unstimulated adhesion was not affected. To test whether PGE1 acted primarily on T-cells or on EC, they were separately pretreated with PGE1 prior to the adhesion assay. Selective PGE1 pretreatment of eEnd.2, but not of TK-1 dose-dependently inhibited TNF alpha, stimulated T-cell adhesion. Since binding of TK-1 to TNF alpha-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 TNF alpha-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 PGE1. We conclude that PGE1 supresses T-cell adhesion to EC by selectively inhibiting TNF alpha-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.
Weiss
J M
JM
Department of Dermatology, University of Freiburg, Germany.
Pilarski
K A
KA
Weyl
A
A
Peschen
M
M
Schöpf
E
E
Vestweber
D
D
Vanscheidt
W
W
Simon
J C
JC
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D051379:Mice; D012867:Skin / Q000166:cytology / Q000187:drug effects; D012879:Skin Physiological Phenomena; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000527:Alprostadil