The anti-inflammatory actions of platelet endothelial cell adhesion molecule-1 do not involve regulation of endothelial cell NF-kappa B.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Privratsky, JR; Tourdot, BE; Newman, DK; Newman, PJ

Published Date

  • March 2010

Published In

Volume / Issue

  • 184 / 6

Start / End Page

  • 3157 - 3163

PubMed ID

  • 20173029

Pubmed Central ID

  • 20173029

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.0901944

Language

  • eng