VASCULAR ENDOTHELIAL PLATELET ENDOTHELIAL-CELL 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 const itutively expressed by vascular endothelium and concentrates at interc ellular junctions. Regulation of PECAM-1 expression on endothelial cel ls may modulate leukocyte trafficking, angiogenesis, and vascular perm eability. 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 mi crovascular endothelial cells. Northern blot analysis revealed express ion of PECAM-1 mRNA transcripts in endothelial cells derived from bovi ne aorta, bovine glomeruli, and human umbilical vein under basal condi tions. Treatment of endothelial cells with TNF-alpha and/or IFN-gamma led to dramatic decreases in steady-state levels of PECAM-1 mRNA trans cripts. In contrast, reciprocal induction of ICAM-1 mRNA was evident. Actinomycin D chase experiments demonstrated that cytokines selectivel y destabilize PECAM-1 mRNA transcripts in bovine endothelial cells, de creasing the PECAM-1 mRNA transcript t(1/2) from basal values of 15 +/ - 2 h to 4 +/- 1 h in TNF-alpha- and IFN-gamma-treated cells (p < 0.00 5), an effect that appeared to be independent of new protein synthesis . Nuclear run-off analysis demonstrated no change in the rates of PECA M-1 gene transcription in response to cytokine treatment. Immunoblots and quantitative indirect immunofluorescence indicated decreased total cellular and cell-surface PECAM-1 protein expression following cytoki ne treatment. These findings provide evidence for cytokine-induced rec iprocal regulation of transcripts of Ig-like adhesion molecules on vas cular endothelium.