HIV-1 Tat-mediated induction of platelet-derived growth factor in astrocytes: role of early growth response gene 1.
Title | HIV-1 Tat-mediated induction of platelet-derived growth factor in astrocytes: role of early growth response gene 1. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Bethel-Brown, C, Yao, H, Callen, S, Lee, YHan, Dash, PK, Kumar, A, Buch, S |
Journal | J Immunol |
Volume | 186 |
Issue | 7 |
Pagination | 4119-29 |
Date Published | 2011 Apr 1 |
ISSN | 1550-6606 |
Keywords | Animals, Astrocytes, Cell Line, Tumor, Cell Proliferation, Early Growth Response Protein 1, External, HIV-1, Humans, Inflammation Mediators, Platelet-Derived Growth Factor, Proto-Oncogene Proteins c-sis, Rats, Rats, Sprague-Dawley, Recombinant Proteins, tat Gene Products, Human Immunodeficiency Virus, Up-Regulation |
Abstract | HIV-associated neurologic disorders (HAND) are estimated to affect almost 60% of HIV-infected individuals. HIV encephalitis, the pathologic correlate of the most severe form of HAND, is often characterized by glial activation, cytokine-chemokine dysregulation, and neuronal damage and loss. However, the severity of HIV encephalitis correlates better with glial activation rather than viral load. Using the macaque model, it has been demonstrated that SIV encephalitis correlates with increased expression of the mitogen platelet-derived growth factor (PDGF) B chain in the brain. The goal of this study was to explore the role of PDGF-B chain in HIV-associated activation and proliferation of astrocytes. Specifically, the data demonstrate that exposure of rat and human astrocytes to the HIV-1 protein Tat resulted in the induction of PDGF at both the mRNA and protein levels. Furthermore, PDGF-BB induction was regulated by activation of ERK1/2 and JNK signaling pathways and the downstream transcription factor early growth response 1. Chromatin immunoprecipitation assays demonstrated binding of Egr-1 to the PDGF-B promoter. Exposure of astrocytes to PDGF-BB in turn led to increased proliferation and the release of proinflammatory cytokines MCP-1 and IL-1β. Because astrogliosis is linked to disease severity, understanding its regulation by PDGF-BB could aid in the development of therapeutic intervention strategies for HAND. |
DOI | 10.4049/jimmunol.1002235 |
Alternate Journal | J. Immunol. |
PubMed ID | 21368226 |
PubMed Central ID | PMC3110059 |
Grant List | 5U01MH083500 / MH / NIMH NIH HHS / United States A024442 / / PHS HHS / United States DA020392 / DA / NIDA NIH HHS / United States DA023397 / DA / NIDA NIH HHS / United States DA027729 / DA / NIDA NIH HHS / United States MH-068212 / MH / NIMH NIH HHS / United States N01MH32002 / MH / NIMH NIH HHS / United States NS38841 / NS / NINDS NIH HHS / United States P30 MH062261 / MH / NIMH NIH HHS / United States R01 DA020392 / DA / NIDA NIH HHS / United States R01 DA020392-04 / DA / NIDA NIH HHS / United States R01 DA020392-05 / DA / NIDA NIH HHS / United States R01 MH068212 / MH / NIMH NIH HHS / United States R01 MH068212-09 / MH / NIMH NIH HHS / United States R01 MH068212-10 / MH / NIMH NIH HHS / United States R24MH59724 / MH / NIMH NIH HHS / United States R24MH59745 / MH / NIMH NIH HHS / United States R24NS45491 / NS / NINDS NIH HHS / United States U01MH083501 / MH / NIMH NIH HHS / United States U01MH083545 / MH / NIMH NIH HHS / United States U0MH083506 / MH / NIMH NIH HHS / United States U0MH083507 / MH / NIMH NIH HHS / United States |