Author:
Liu Kai,Chi David S.,Li Chuanfu,Hall H. Kenton,Milhorn Denise M.,Krishnaswamy Guha
Abstract
Expression of cell adhesion molecule in endothelial cells upon activation by human immunodeficiency virus (HIV) infection is associated with the development of atherosclerotic vasculopathy. We postulated that induction of vascular cell adhesion molecule-1 (VCAM-1) by HIV-1 Tat protein in endothelial cells might represent an early event that could culminate in inflammatory cell recruitment and vascular injury. We determined the role of HIV-1 Tat protein in VCAM-1 expression in human pulmonary artery endothelial cells (HPAEC). HIV-1 Tat protein treatment significantly increased cell-surface expression of VCAM-1 in HPAEC. Consistently, mRNA expression of VCAM-1 was also increased by HIV-1 Tat protein as measured by RT-PCR. HIV-1 Tat protein-induced VCAM-1 expression was abolished by the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) and the p38 MAPK inhibitor SB-203580. Furthermore, HIV-1 Tat protein enhanced DNA binding activity of NF-κB, facilitated nuclear translocation of NF-κB subunit p65, and increased production of reactive oxygen species (ROS). Similarly to VCAM-1 expression, HIV-1 Tat protein-induced NF-κB activation and ROS generation were abrogated by PDTC and SB-203580. These data indicate that HIV-1 Tat protein is able to induce VCAM-1 expression in HPAEC, which may represent a pivotal early molecular event in HIV-induced vascular/pulmonary injury. These data also suggest that the molecular mechanism underlying the HIV-1 Tat protein-induced VCAM-1 expression may involve ROS generation, p38 MAPK activation, and NF-κB translocation, which are the characteristics of pulmonary endothelial cell activation.
Publisher
American Physiological Society
Subject
Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology
Reference46 articles.
1. Inhibitors of HIV-1 Gene Expression and Transcription
2. Cardiovascular Manifestations of HIV Infection
3. Human Immunodeficiency Virus Type 1 Infection Modulates the Interleukin (IL)–1β and IL‐6 Responses of Human Macrophages to CD40 Ligand Stimulation
4. Bohan CA, Kashanchi F, Ensoli B, Buonaguro L, Boris-Lawrie KA, and Brady JN.Analysis of tat transactivation of human immunodeficiency virus transcription in vitro.Gene Expr2: 391–407, 1992.
5. Bondmass M.The cardiac manifestations of acquired immune deficiency syndrome and nursing implications.Medsurg Nurs3: 42–48, 1994.
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