TY - JOUR
T1 - Tumor necrosis factor-alpha up-regulates the expression of beta1,4-galactosyltransferase I in primary human endothelial cells by mRNA stabilization
AU - Garcia Vallejo, J.J.
AU - van Dijk, W.
AU - van Die, I.M.
AU - Gringhuis, S.I.
PY - 2005
Y1 - 2005
N2 - During the course of an inflammatory response, the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFalpha) triggers endothelial cells to increase the expression levels of adhesion molecules that are pivotal for the rolling, adhesion, and transmigration of leukocytes over the endothelial cell wall. Here we show that TNFalpha, in addition, has a regulatory function in the biosynthesis of proper carbohydrate molecules on endothelial cells that constitute ligands for adhesion molecules on leukocytes. Our data show that TNFalpha induced an increase in the expression of beta1,4-galactosyltransferase-1 (beta4GalT-1) in primary human umbilical vein endothelial cells in a time- and concentration-dependent manner. The beta4GalT-1 mRNA up-regulation correlated with an increase in the Golgi expression and catalytic activity of the enzyme. Furthermore, an enhanced incorporation of galactose was observed in newly synthesized glycoproteins. Analysis of the molecular mechanism behind the up-regulation of beta4GalT-1 showed that the increase in mRNA levels is due to an enhanced stability of the transcripts. These data strongly demonstrate that TNFalpha modulates the glycosylation of endothelial cells by a mechanism that directly enhances the stability of beta4GalT-1 mRNA transcripts
AB - During the course of an inflammatory response, the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFalpha) triggers endothelial cells to increase the expression levels of adhesion molecules that are pivotal for the rolling, adhesion, and transmigration of leukocytes over the endothelial cell wall. Here we show that TNFalpha, in addition, has a regulatory function in the biosynthesis of proper carbohydrate molecules on endothelial cells that constitute ligands for adhesion molecules on leukocytes. Our data show that TNFalpha induced an increase in the expression of beta1,4-galactosyltransferase-1 (beta4GalT-1) in primary human umbilical vein endothelial cells in a time- and concentration-dependent manner. The beta4GalT-1 mRNA up-regulation correlated with an increase in the Golgi expression and catalytic activity of the enzyme. Furthermore, an enhanced incorporation of galactose was observed in newly synthesized glycoproteins. Analysis of the molecular mechanism behind the up-regulation of beta4GalT-1 showed that the increase in mRNA levels is due to an enhanced stability of the transcripts. These data strongly demonstrate that TNFalpha modulates the glycosylation of endothelial cells by a mechanism that directly enhances the stability of beta4GalT-1 mRNA transcripts
U2 - https://doi.org/10.1074/jbc.M410093200
DO - https://doi.org/10.1074/jbc.M410093200
M3 - Article
C2 - 15668241
SN - 0021-9258
VL - 280
SP - 12676
EP - 12682
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 13
ER -