IFN-gamma regulates the expression of the adhesion molecule ELAM-1 and IL-6 production by human endothelial cells in vitro.
In this study two new in vitro effects of IFN-gamma on human umbilical vein endothelial (HUVE) cells were described. First, it was shown that the expression of the adhesion molecule ELAM-1 on activated HUVE cells can be modulated by IFN-gamma. ELAM-1 is normally not expressed by HUVE cells, but its expression can rapidly be induced by TNF, IL-1, or LPS. Maximal expression is reached after 4 to 6 h of activation, and after 24 h the expression disappeared. Whereas IFN-gamma per se did not induce expression of ELAM-1, it enhanced and prolonged the expression of ELAM-1. This enhancement occurred when IFN-gamma was added before activation as well as when added simultaneously with activation. When IFN-gamma was added 6 or 9 h after the activation, the normally ongoing reduction of expression was not only retarded, but the expression increased for at least 3 h. Moreover, IFN-gamma abrogated the refractory period for restimulation. Neither IFN-beta nor IL-6 had any effect on the expression of ELAM-1. The second effect of IFN-gamma on HUVE cells is the capacity to enhance the IL-6 production by these cells. Prestimulation as well as coincubation of IFN-gamma with TNF, IL-1, or LPS resulted in a strongly augmented production of IL-6. The effects of IFN-gamma may in vivo play a role in the regulation of an inflammatory reaction, because ELAM-1 is an adhesion molecule for neutrophils, and IL-6 has an enhancing effect on the cytotoxicity of neutrophils.
Leeuwenberg
J F
JF
Department of Surgery, University of Limburg, Maastricht, The Netherlands.
von Asmuth
E J
EJ
Jeunhomme
T M
TM
Buurman
W A
WA
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D011994:Recombinant Proteins; D013997:Time Factors
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007370:Interferon Type I; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007371:Interferon-gamma