The Human Immunodeficiency Virus-1 Tat Protein Activates Human Umbilical Vein Endothelial Cell E-selectin Expression via an NF-κB-dependent Mechanism

Abstract

Human immunodeficiency virus infection is associ-

αvβ3-integrin-dependent activation of focal adhesion kinase mediates NF-κB activation and motogenic activity by HIV-1 Tat in endothelial cells

“…Here, we show that NF-B is activated in ECs following extracellular interaction of Tat with ␣ v ␤ 3 and the consequent activation of FAK, RhoA and pp60 src . In ECs, NF-B activation by Tat has, to date, been connected to the overexpression of surface adhesive molecules and/or activation of inflammatory pathways (Cooper et al, 1996;Cota-Gomez et al, 2002;Pieper et al, 2002;Toborek et al, 2003). The data here reported implicate NF-B in the motogenic activity exerted by Tat in vitro, suggesting its involvement also in the neovascularization induced by Tat in vivo.…”

“…Tat has been shown to activate NF-B in different cell types including astrocytes (Conant et al, 1998), macrophages (Kumar et al, 1999), T-cells (Li-Weber et al, 2000) and ECs (Cooper et al, 1996;Cota-Gomez et al, 2002;Pieper et al, 2002;Toborek et al, 2003), but the mechanism(s) of activation are not fully elucidated. Indeed, Tat can induce NF-B activation both when administered extracellularly (Cota-Gomez et al, 2002) and when produced endogenously…”

p47 Participates in Activation of RelA in Endothelial Cells

“…pGEX-RelA-PR was constructed by amplification of RelA (301-431) between BamHI and EcoRI sites and ligation into pGEX-2TK. pELAMluc was previously described (23). p67…”

Pathogenesis of HIV-Associated Pulmonary Hypertension: Potential Role of HIV-1 nef

“…Similar to severe PH, inflammatory cells are present in the perivasculature of HIV tissues, suggesting that HIV-induced chronic inflammation and immune hyperactivation may enrich the proinflammatory milieu implicated in HIV-PH. Viral proteins such as Nef and Tat have been shown to lead to endothelial dysfunction and increased inflammation through activation of adhesion molecules and production of inflammatory chemokines, independent of virus production (21)(22)(23)(24)(25).…”