The anti-inflammatory actions of platelet endothelial cell adhesion molecule-1 do not involve regulation of endothelial cell NF-kappa B. J Immunol 2010 Mar 15;184(6):3157-63
Date
02/23/2010Pubmed ID
20173029Pubmed Central ID
PMC3628820DOI
10.4049/jimmunol.0901944Scopus ID
2-s2.0-77951928514 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
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.
Author List
Privratsky JR, Tourdot BE, Newman DK, Newman PJAuthors
Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of WisconsinDebra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Active Transport, Cell NucleusBlood Platelets
Cell Line
Cells, Cultured
Chemotaxis, Leukocyte
Endothelium, Vascular
Humans
Inflammation Mediators
Leukocytes
NF-kappa B
Platelet Endothelial Cell Adhesion Molecule-1
Signal Transduction
Transcription, Genetic