Modulation of pyrogen-induced upregulation of endothelial cell adhesion molecules (CAMs) by interleukin-4: transcriptional mechanisms and CAM-shedding.
The pyrogens interleukin 1 (IL-1), tumor necrosis factor (TNF), and bacterial lipopolysaccharides (LPS) are known to increase endothelial cell (EC) adhesiveness for leukocytes by stimulating surface expression of various adhesion molecules. IL-4, a product of activated T-cells, was shown to affect pyrogen-mediated regulation of EC adhesion molecule surface expression. In the present study, we investigated the effect of IL-4 on pyrogen-induced upregulation of the cell adhesion molecules (CAMs) ICAM-1 (intercellular cell adhesion molecule-1), ELAM-1 (endothelial leucocyte adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1) in cultured human umbilical vein EC (HUVEC). Surface expression of adhesion molecules was quantified by flow cytometry, HUVEC mRNA content was estimated by Northern blot analysis, and ICAM-1 antigen in conditioned media was measured by ELISA. Incubation of HUVEC with IL-1 (100 U/ml), TNF (500 U/ml), and LPS (10 micrograms/ml) caused significant increase in ICAM-1, ELAM-1, and VCAM-1 surface expression; IL-1 caused about an eightfold increase in ICAM-1 expression, about a 13-fold increase in ELAM-1 surface expression, and about a fourfold increase in VCAM-1 expression. Coincubation of pyrogens with IL-4 (500 U/ml) differentially influenced their proadhesive effects on the HUVEC surface. In the presence of IL-4, IL-1-induced ICAM-1 upregulation was reduced, ELAM-1 upregulation was not significantly influenced by IL-4, and induction of VCAM-1 was enhanced by IL-4.(ABSTRACT TRUNCATED AT 250 WORDS)
Kapiotis
S
S
Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Austria.
Quehenberger
P
P
Sengoelge
G
G
Pärtan
C
C
Eher
R
R
Strobl
H
H
Bevec
D
D
Zapolska
D
D
Schwarzinger
I
I
Speiser
W
W
D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000378:metabolism*; D004926:Escherichia coli; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D011749:Pyrogens / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011749:Pyrogens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4