Vascular endothelial platelet endothelial adhesion molecule-1 (PECAM-1) expression is decreased by TNF-alpha and IFN-gamma. Evidence for cytokine-induced destabilization of messenger ribonucleic acid transcripts in bovine endothelial cells.
Platelet endothelial cell-adhesion molecule-1 (PECAM-1, CD31) is constitutively expressed by vascular endothelium and concentrates at intercellular junctions. Regulation of PECAM-1 expression on endothelial cells may modulate leukocyte trafficking, angiogenesis, and vascular permeability. Given that cytokine activation induces profound alterations in endothelial phenotype, studies sought to determine whether cytokine treatment modulated PECAM-1 mRNA and protein content in macro- and microvascular endothelial cells. Northern blot analysis revealed expression of PECAM-1 mRNA transcripts in endothelial cells derived from bovine aorta, bovine glomeruli, and human umbilical vein under basal conditions. Treatment of endothelial cells with TNF-alpha and/or IFN-gamma led to dramatic decreases in steady-state levels of PECAM-1 mRNA transcripts. In contrast, reciprocal induction of ICAM-1 mRNA was evident. Actinomycin D chase experiments demonstrated that cytokines selectively destabilize PECAM-1 mRNA transcripts in bovine endothelial cells, decreasing the PECAM-1 mRNA transcript t1/2 from basal values of 15 +/- 2 h to 4 +/- 1 h in TNF-alpha- and IFN-gamma-treated cells (p < 0.005), an effect that appeared to be independent of new protein synthesis. Nuclear run-off analysis demonstrated no change in the rates of PECAM-1 gene transcription in response to cytokines treatment. Immunoblots and quantitative indirect immunofluorescence indicated decreased total cellular and cell-surface PECAM-1 protein expression following cytokine treatment. These findings provide evidence for cytokine-induced reciprocal regulation of transcripts of Ig-like adhesion molecules on vascular endothelium.
Stewart
R J
RJ
Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada.
Kashour
T S
TS
Marsden
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D001483:Base Sequence; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000302:isolation & purification; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma