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-1β and TNFα). Cell lysate fractions were analyzed for MAP Kinase activity and NFκB 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 TNFα acting on the production of IL-6. When HPAEC were stimulated with IL-1β and TNFα, peak phosphorylation of p38 MAP Kinase was found at 45 minutes, while NFκB was maximally activated at two hours. Both the ERK1,2 and p38 cascades of MAP Kinase were activated by tat, and an increase in NFκB 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.
","abstract_html":"<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-1β and TNFα). Cell lysate fractions were analyzed for MAP Kinase activity and NFκB 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 TNFα acting on the production of IL-6. When HPAEC were stimulated with IL-1β and TNFα, peak phosphorylation of p38 MAP Kinase was found at 45 minutes, while NFκB was maximally activated at two hours. Both the ERK1,2 and p38 cascades of MAP Kinase were activated by tat, and an increase in NFκB 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>","abstract_has_math":false,"creators":["Henry, Jason L."],"institution":null,"degree_name":"MS (Master of Science)","degree_level":"Thesis - unrestricted","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2002,"date_issued":"2002-08-16T07:00:00Z","date_published":"2002-08-16T07:00:00Z","updated_at":"2026-07-24T02:19:07Z","subjects":["HIV","gp120","endothelium","tat","cytokine","IL-6","IL-8","NFkB","Medical Sciences","Medicine and Health Sciences"],"languages":[],"rights":["Copyright by the authors."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.etsu.edu/etd/677","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Henry, Jason L."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2002-08-16T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis - unrestricted"]},{"key":"thesis:degree_name","label":"Degree Name","values":["MS (Master of Science)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["HIV","gp120","endothelium","tat","cytokine","IL-6","IL-8","NFkB","Medical Sciences","Medicine and Health Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["Copyright by the authors."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.etsu.edu/context/etd/article/1834/viewcontent/HenryJ050302a.pdf","https://dc.etsu.edu/etd/677"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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-1β and TNFα). Cell lysate fractions were analyzed for MAP Kinase activity and NFκB 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 TNFα acting on the production of IL-6. When HPAEC were stimulated with IL-1β and TNFα, peak phosphorylation of p38 MAP Kinase was found at 45 minutes, while NFκB was maximally activated at two hours. Both the ERK1,2 and p38 cascades of MAP Kinase were activated by tat, and an increase in NFκB 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.
"]},{"key":"dc:title","label":"Title","values":["HIV Tat Protein Activates Endothelial Cells through NFκB and MAP Kinase Pathways."]}]}],"canonical_facts":{"dc:creator":["Henry, Jason L."],"dc:date.issued":["2002-08-16T07:00:00Z"],"dc:description.abstract":["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-1β and TNFα). Cell lysate fractions were analyzed for MAP Kinase activity and NFκB 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 TNFα acting on the production of IL-6. When HPAEC were stimulated with IL-1β and TNFα, peak phosphorylation of p38 MAP Kinase was found at 45 minutes, while NFκB was maximally activated at two hours. Both the ERK1,2 and p38 cascades of MAP Kinase were activated by tat, and an increase in NFκB 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.
"],"dc:identifier":["https://dc.etsu.edu/context/etd/article/1834/viewcontent/HenryJ050302a.pdf","https://dc.etsu.edu/etd/677"],"dc:rights":["Copyright by the authors."],"dc:subject":["HIV","gp120","endothelium","tat","cytokine","IL-6","IL-8","NFkB","Medical Sciences","Medicine and Health Sciences"],"dc:title":["HIV Tat Protein Activates Endothelial Cells through NFκB and MAP Kinase Pathways."],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Thesis - unrestricted"],"thesis:degree_name":["MS (Master of Science)"]},"updated_at":"2026-07-24T02:19:07Z"}