The anti-inflammatory actions of platelet endothelial cell adhesion molecule-1 do not involve regulation of endothelial cell NF-kappa B.
PECAM-1 is a cell adhesion and signaling receptor that is expressed on many hematopoietic cells and at endothelial cell-cell junctions. Accumulating evidence from a number of in vitro and in vivo model systems suggests that PECAM-1 suppresses cytokine production and vascular permeability induced by a wide range of inflammatory stimuli. In several of these models of inflammatory disease, endothelial, and not leukocyte or platelet, PECAM-1 conferred protection against inflammatory insult. However, the mechanism by which endothelial PECAM-1 functions as an anti-inflammatory protein is poorly understood. It was recently suggested that PECAM-1 exerts its anti-inflammatory effects in endothelial cells by inhibiting the activity of NF-kappaB, a proinflammatory transcription factor. To confirm and extend these observations, we examined the effect of engaging, cross-linking, or expressing PECAM-1 on NF-kappaB activation in a variety of human cells. PECAM-1 had no effect on the phosphorylation of the NF-kappaB inhibitory protein, IkappaBalpha; on the nuclear translocation of NF-kappaB; on the suppression of cytokine-induced transcriptional activation of an NF-kappaB luciferase reporter plasmid; or on the cytokine-stimulated upregulation of ICAM-1, an NF-kappaB target gene, in endothelial cells. Taken together, these studies strongly suggest that the anti-inflammatory actions of PECAM-1 in endothelial cells are not likely to involve its regulation of NF-kappaB.
Privratsky
Jamie R
JR
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201, USA.
Tourdot
Benjamin E
BE
Newman
Debra K
DK
Newman
Peter J
PJ
D021581:Active Transport, Cell Nucleus / Q000235:genetics / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
D018836:Inflammation Mediators; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1