TY - JOUR
T1 - Endotoxin, tumor necrosis factor, and dexamethasone effects on human endothelial cell fibronectin dynamics
T2 - synthesis, matrix assembly, and receptor expression.
AU - Romer, L. H.
AU - Polin, R. A.
PY - 1995
Y1 - 1995
N2 - The three inflammatory modulators endotoxin, tumor necrosis factor (TNF) alpha, and dexamethasone (DEX) were studied for their effects on fibronectin (FN) dynamics in human umbilical vein endothelial cells. Cell culture supernatants were analyzed for new soluble pool FN synthesis. Endotoxin (LPS) (10 micrograms/mL) decreased the newly synthesized soluble pool of FN (p < 0.05). An increase in soluble FN was demonstrated with 1 and 10 ng/mL TNF alpha (p < 0.05). DEX decreased newly synthesized endothelial cell (EC) FN in the soluble pool at 4, 40, and 400 micrograms/mL (p < 0.05). Extracellular matrix FN content was examined using immunofluorescence. The thick FN mesh seen in control cells contrasted with a decreased FN matrix after treatment with each of the three study agents. Immunoprecipitation of the FN receptor alpha 5 beta 1 integrin from [35S]methionine-labelled cell extracts demonstrated down regulation of receptor expression by both TNF alpha and DEX as compared with control samples. These data indicate that LPS, TNF alpha, and DEX may weaken EC-substratum adhesion by differential effects on FN synthesis and secretion, FN incorporation into the extracellular matrix, and down regulation of FN receptor expression.
AB - The three inflammatory modulators endotoxin, tumor necrosis factor (TNF) alpha, and dexamethasone (DEX) were studied for their effects on fibronectin (FN) dynamics in human umbilical vein endothelial cells. Cell culture supernatants were analyzed for new soluble pool FN synthesis. Endotoxin (LPS) (10 micrograms/mL) decreased the newly synthesized soluble pool of FN (p < 0.05). An increase in soluble FN was demonstrated with 1 and 10 ng/mL TNF alpha (p < 0.05). DEX decreased newly synthesized endothelial cell (EC) FN in the soluble pool at 4, 40, and 400 micrograms/mL (p < 0.05). Extracellular matrix FN content was examined using immunofluorescence. The thick FN mesh seen in control cells contrasted with a decreased FN matrix after treatment with each of the three study agents. Immunoprecipitation of the FN receptor alpha 5 beta 1 integrin from [35S]methionine-labelled cell extracts demonstrated down regulation of receptor expression by both TNF alpha and DEX as compared with control samples. These data indicate that LPS, TNF alpha, and DEX may weaken EC-substratum adhesion by differential effects on FN synthesis and secretion, FN incorporation into the extracellular matrix, and down regulation of FN receptor expression.
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U2 - 10.1139/o95-057
DO - 10.1139/o95-057
M3 - Article
C2 - 8703422
AN - SCOPUS:0029332219
SN - 0829-8211
VL - 73
SP - 515
EP - 524
JO - Biochemistry and cell biology = Biochimie et biologie cellulaire
JF - Biochemistry and cell biology = Biochimie et biologie cellulaire
IS - 7-8
ER -