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Selective enhancement of endothelial cell VCAM‐1 expression by interleukin‐10 in the presence of activated leucocytes
Author(s) -
FIEHN C.,
PALEOLOG E. M.,
FELDMANN M.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00286.x
Subject(s) - endothelial stem cell , cell adhesion molecule , biology , endothelium , peripheral blood mononuclear cell , cytokine , proinflammatory cytokine , microbiology and biotechnology , immunology , inflammation , in vitro , endocrinology , biochemistry
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.