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HIV-1 Tat-mediated induction of platelet-derived growth factor in astrocytes: role of early growth response gene 1.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Apr 01; Vol. 186 (7), pp. 4119-29. Date of Electronic Publication: 2011 Mar 02. - Publication Year :
- 2011
-
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.
- Subjects :
- Animals
Astrocytes pathology
Becaplermin
Cell Line, Tumor
Cell Proliferation
Early Growth Response Protein 1 biosynthesis
Early Growth Response Protein 1 physiology
HIV-1 immunology
Humans
Inflammation Mediators metabolism
Inflammation Mediators physiology
Platelet-Derived Growth Factor genetics
Proto-Oncogene Proteins c-sis
Rats
Rats, Sprague-Dawley
Recombinant Proteins biosynthesis
Recombinant Proteins genetics
Up-Regulation genetics
Up-Regulation immunology
Astrocytes immunology
Astrocytes metabolism
Early Growth Response Protein 1 genetics
Platelet-Derived Growth Factor biosynthesis
tat Gene Products, Human Immunodeficiency Virus physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 186
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 21368226
- Full Text :
- https://doi.org/10.4049/jimmunol.1002235