ABSTRACT
VCAM-1) expressed from both leukocytes and vascular endothelium (Carlos and Harlan 1994, Haverslag et al. 2008). During recent years, eff orts have intensifi ed to elucidate the links between activation of PI3K/Akt-NF-κB signaling transduction pathways and the regulation of gene expression of adhesion molecules. However, up to now, very few comprehensive studies have investigated the molecular signaling interaction between the PI3K and NF-κB pathways in infl ammatory cytokineelicited upregulation of VCAM-1 at the levels of gene promoter, PI3K activity, and NF-κB modulation, simultaneously. Further understanding of the crosstalk and interaction between vascular endothelial cells and infl ammatory leukocytes will lead us to new avenues for the prevention and therapy of infl ammatory and cardiovascular diseases as well as cancer. One of the crucial proteins is VCAM-1, a member of the Ig superfamily that mediates leukocyte binding to the endothelial cell through its interaction with the leukocyte’s integrin counterreceptor very late activation antigen 4 (VLA-4). Because of the selective expression of VLA-4 on monocytes and lymphocytes, but not neutrophils, VCAM-1 plays an important role in mediating mononuclear leukocyte-selective adhesion. However, the molecular mechanisms of VCAM-1 upregulation in the infl ammatory pulmonary system are still not completely understood. We investigated the eff ects of an infl ammatory cytokine, HIMF, in the regulation of VCAM-1 expression and the results showed that VCAM-1 gene expression is closely controlled by HIMF-induced PI3K/AktNF-κB activation (Tong et al. 2006). Blocking PI3K/Akt activity or inhibiting NFκB activation with, respectively, mutant dominant negative proteins or chemical inhibitors signifi cantly prevented VCAM-1 gene upregulation. Th ese fi ndings certainly provided a typical example for infl ammatory cytokine-induced adhesion molecule overproduction and further facilitate our understanding of the process of leukocyte-endothelium interaction and infl ammatory cell migration.
