TY - JOUR
T1 - TGF-beta downmodulates cytokine-induced monocyte chemoattractant protein (MCP)-1 expression in human endothelial cells. A putative role for TGF-beta in the modulation of TNF receptor expression
AU - Weiss, Jonathan M.
AU - Cuff, Carolyn A.
AU - Berman, Joan W.
N1 - Funding Information:
We thank Drs. Hsiao-Nan Hao and Karen Weiden-heim for providing the fetal tissue used for these experiments and Dr. C. Chang for assistance with the statistical analyses. We thank Dr. Celia Brosnan for her most helpful discussions. We thank Dr. Tina Calderon and Neelufar Mozaffarian for their critical reading of this manuscript. The FACS facility at the Albert Einstein College of Medicine is supported, in part, by NCI Cancer Center Support Grant fiP30-CA13330. This manuscript is in partial fulfillment for the degree of Doctor of Philosophy from the Sue Golding Graduate Division of the Albert Einstein College of Medicine for J.M.W. This work was supported in part by NIMH Grant MH52974, NIH Grants 11920 and 5T32CA09173.
PY - 1999
Y1 - 1999
N2 - The expression of chemokines, including monocyte chemoattractant protein (MCP)-1, by many cell types contributes to the pathogenesis of inflammatory diseases. We examined MCP-1 expression in human umbilical vein endothelial cells (EC) following cytokine treatment. We specifically compared the effect of TGF-β1 on this cytokine-induced expression, as TGF-β has been shown to have immunosuppressive effects on EC. EC expressed MCP-1 mRNA and protein in response to TNFα, IFNγ or IL-1β, but not TGF-β1. TGF-β1 in cotreatment with either TNFα or IL-1β, but not IFNγ, significantly decreased MCP-1 mRNA and protein expression, as compared to TNFα or IL-1β treatment alone. Pretreatment with TGF-β had no effect on any cytokine-induced MCP-1 expression. TGF-β had no effect on MCP-1 mRNA stability. Examination of TNF receptor expression by flow cytometry revealed that TNFα treatment caused a decrease of p75 expression on the cell surface. The p55 receptor was not detected at the cell surface, but was localized intracellularly by confocal microscopy. Treatment of EC with TGF-β alone decreased p75 surface expression and in cotreatment with TNFα, caused an additive decrease in p75 surface expression, as compared to TNFα treatment alone. Whereas mRNA expression for both receptors was increased with TNFα treatment, this was decreased with TGF-β/TNFα cotreatment, as compared to TNFα treatment alone. Thus, the expression of TNF receptors was also down-modulated by TGF-β. These findings indicate additional mechanisms by which TGF-β exerts immunosuppressive properties on EC.
AB - The expression of chemokines, including monocyte chemoattractant protein (MCP)-1, by many cell types contributes to the pathogenesis of inflammatory diseases. We examined MCP-1 expression in human umbilical vein endothelial cells (EC) following cytokine treatment. We specifically compared the effect of TGF-β1 on this cytokine-induced expression, as TGF-β has been shown to have immunosuppressive effects on EC. EC expressed MCP-1 mRNA and protein in response to TNFα, IFNγ or IL-1β, but not TGF-β1. TGF-β1 in cotreatment with either TNFα or IL-1β, but not IFNγ, significantly decreased MCP-1 mRNA and protein expression, as compared to TNFα or IL-1β treatment alone. Pretreatment with TGF-β had no effect on any cytokine-induced MCP-1 expression. TGF-β had no effect on MCP-1 mRNA stability. Examination of TNF receptor expression by flow cytometry revealed that TNFα treatment caused a decrease of p75 expression on the cell surface. The p55 receptor was not detected at the cell surface, but was localized intracellularly by confocal microscopy. Treatment of EC with TGF-β alone decreased p75 surface expression and in cotreatment with TNFα, caused an additive decrease in p75 surface expression, as compared to TNFα treatment alone. Whereas mRNA expression for both receptors was increased with TNFα treatment, this was decreased with TGF-β/TNFα cotreatment, as compared to TNFα treatment alone. Thus, the expression of TNF receptors was also down-modulated by TGF-β. These findings indicate additional mechanisms by which TGF-β exerts immunosuppressive properties on EC.
KW - Endothelial cells
KW - Monocyte chemoattractant protein-1
KW - TNF receptors
KW - Transforming growth factor-beta
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U2 - 10.3109/10623329909078496
DO - 10.3109/10623329909078496
M3 - Article
C2 - 10475092
AN - SCOPUS:0032838418
SN - 1062-3329
VL - 6
SP - 291
EP - 302
JO - Endothelium: Journal of Endothelial Cell Research
JF - Endothelium: Journal of Endothelial Cell Research
IS - 4
ER -