Selective enhancement of endothelial cell VCAM-1 expression by interleukin-10 in the presence of activated leucocytes.
Although initially described as an immunomodulatory cytokine, interleukin-10 (IL-10) has also been proposed to exert proinflammatory effects both in vivo and in vitro. In particular, studies in IL-10 transgenic mice have suggested that IL-10 may activate vascular endothelium to promote leucocyte adhesion and extravasation. In the present study we investigated whether IL-10 activates endothelial cells either directly or indirectly, via signals produced by leucocytes in the endothelial cell environment, using a co-culture of human umbilical vein endothelial cells and peripheral blood mononuclear cells (PBMC). No direct effects of IL-10 on endothelial cell responses were observed. However, in the presence of phytohaemagglutinin-activated PBMC, IL-10 increased the expression on endothelial cells of vascular cell adhesion molecule-1 (VCAM-1) but not of intercellular adhesion molecule-1, E-selectin or major histocompatibility complex (MHC) antigens, an effect mediated by PBMC-derived soluble factors. We also observed that interferon-gamma (IFN-gamma) antagonized VCAM-1 expression on endothelial cells mediated by IL-4 and IL-13. Since IL-10 has previously been documented to down-regulate release of IFN-gamma by PBMC, we propose that the IL-10-mediated reduction of IFN-gamma production by PBMC results in enhanced responsiveness of endothelial cells to PBMC-derived IL-4 and IL-13, and thus increased expression of VCAM-1. Our results suggest that the relative balance of cytokines produced by infiltrating cells in developing inflammatory lesions may differentially modulate endothelial responsiveness in vivo, and that IL-10 might indirectly stabilize VCAM-1 expression on endothelial cells by affecting the balance of leucocyte-derived cytokines in the endothelial environment.
Fiehn
C
C
Kennedy Institute of Rheumatology, London, UK.
Paleolog
E M
EM
Feldmann
M
M
D002450:Cell Communication / Q000276:immunology; D018929:Cell Culture Techniques; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D010835:Phytohemagglutinins / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D018793:Interleukin-13; D010835:Phytohemagglutinins; D019010:Vascular Cell Adhesion Molecule-1; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma