The Anti-Inflammatory Actions of Platelet Endothelial Cell Adhesion Molecule-1 Do Not Involve Regulation of Endothelial Cell NF-κB

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-I 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-kappa B, a proinflammatory transcription factor. To confirm and extend these observations, we examined the effect of engaging, cross-linking, or expressing PECAM-1 on NF-kappa B activation in a variety of human cells. PECAM-1 had no effect on the phosphorylation of the NF-kappa B inhibitory protein, I kappa B alpha; on the nuclear translocation of NF-kappa B; on the suppression of cytokine-induced transcriptional activation of an NF-kappa B luciferase reporter plasmid; or on the cytokine-stimulated upregulation of ICAM-1, an NF-kappa B 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-kappa B. The Journal of Immunology, 2010, 184: 3157-3163.