HIV Tat Protein Activates Endothelial Cells through NFκB and MAP Kinase Pathways.

<p>HIV infection has been shown to predispose patients to accelerated development of heart disease. One mechanism for this pathology may involve endothelial activation either by HIV itself or by its secreted proteins, gp120 (a viral envelope protein) and tat (a protein that upregulates transcription of viral genes). We have studied the effects of gp120 and tat on signaling and production of inflammatory cytokines by Human Pulmonary Artery Endothelial Cells (HPAEC). HPAEC were stimulated at varying time points with combinations of gp120, tat, and monokines (IL-1&#946; and TNF&#945;). Cell lysate fractions were analyzed for MAP Kinase activity and NF&#954;B activation, and culture supernatants were assayed for inflammatory cytokines (IL-6 and IL-8). The production of IL-6 and IL-8 was significantly enhanced by tat but not by gp120. Both gp120 and tat, however, induced significant morphological changes in HPAEC. The only synergy noted was between high levels of tat and TNF&#945; acting on the production of IL-6. When HPAEC were stimulated with IL-1&#946; and TNF&#945;, peak phosphorylation of p38 MAP Kinase was found at 45 minutes, while NF&#954;B was maximally activated at two hours. Both the ERK1,2 and p38 cascades of MAP Kinase were activated by tat, and an increase in NF&#954;B phosphorylation and translocation were noted. We conclude that the HIV tat protein could be involved in inflammatory changes in endothelium leading to the accelerated development of heart disease in HIV patients.</p>

Name thesis:degree_name

MS (Master of Science)

Level thesis:degree_level

Thesis - unrestricted

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.issued

2002

Author dc:creator

• Henry, Jason L.

• HIV
• gp120
• endothelium
• tat
• cytokine
• IL-6
• IL-8
• NFkB
• Medical Sciences
• Medicine and Health Sciences

Statement dc:rights

• Copyright by the authors.

Repository record dc:identifier

https://dc.etsu.edu/etd/677

OAI identifier oai:identifier

oai:dc.etsu.edu:etd-1834