Endothelin-1 modulates the expression of adhesion molecules on fibroblast-like synovial cells (FLS).
Endothelin-1 is known to possess various biological properties. In the present study we have investigated the effects of Endothelin-1 (Et-1) on the expression of adhesion molecules ICAM-1, VCAM-1 and CD-44 by fibroblast-like synoviocytes. Cultured fibroblast-like synoviocytes were treated with Et-1 in the absence or presence of C1306, a specific endothelin-A-receptor antagonist. Cell surface expression of ICAM-1, VCAM-1 and CD-44 was determined by immunofluorescence studies, Cyto-ELISA and FACS-analysis. ICAM-1, VCAM-1 and CD-44 were constitutively expressed on cultured FLS. After incubation with Et-1 the expression of ICAM-1, VCAM-1 and CD-44 increased. The level of expression of adhesion molecules after Et-1 stimulation was similar to cytokine mediated effects (IL-1 beta, TNF-alpha). IL-1 beta showed the strongest stimulatory effect on the expression of ICAM-1, TNF-alpha preferentially induced the expression of VCAM-1 and CD-44, and Et-1 strongly stimulated the upregulation of CD-44 expression. In addition, Et-1 enhanced significantly the IL-1 beta mediated upregulation of VCAM-1 expression, whereas TNF-alpha mediated expression of VCAM-1 was downregulated by Et-1. Furthermore, the Et-1 induced expression of adhesion molecules on FLS was mediated via the endothelin-A-receptor (EtA-receptor), since C-1306, a selective endothelin-A-receptor antagonist, could block this effect. These results indicate that Et-1 has stimulating effects on FLS in vitro. The expression of adhesion molecules can be upregulated by Et-1 similar to proinflammatory cytokines. The modulating effect of Et-1 can be inhibited by the pretreatment with a selective EtA-receptor antagonist. Thus, Et-1 may have immunoregulatory functions in the recruitment of cells infiltrating the inflamed tissue.
Schwarting
A
A
First Department of Medicine, University of Mainz, Germany.
Schlaak
J
J
Lotz
J
J
Pfers
I
I
Meyer zum Büschenfelde
K H
KH
Mayet
W J
WJ
D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000187:drug effects*; D002478:Cells, Cultured; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology; D044022:Receptor, Endothelin A; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects
D015815:Cell Adhesion Molecules; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D018960:Hyaluronan Receptors; D007375:Interleukin-1; D044022:Receptor, Endothelin A; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1