HIV-1 tat-mediated induction of platelet-derived growth factor in astrocytes: Role of early growth response gene 1

Crystal Bethel-Brown, Honghong Yao, Shannon Callen, Young Han Lee, Prasanta K. Dash, Anil Kumar, Shilpa J Buch

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

HIV-associated neurologic disorders (HAND) are estimated to affect almost 60% of HIV-infected individuals. HIVencephalitis, 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 HIVassociated 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.

Original languageEnglish (US)
Pages (from-to)4119-4129
Number of pages11
JournalJournal of Immunology
Volume186
Issue number7
DOIs
StatePublished - Apr 1 2011

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Platelet-Derived Growth Factor
Astrocytes
HIV-1
Proto-Oncogene Proteins c-sis
HIV
Nervous System Diseases
Growth
Genes
Encephalitis
Neuroglia
Early Growth Response Protein 1
Cytokines
Human Immunodeficiency Virus Proteins
MAP Kinase Signaling System
Chromatin Immunoprecipitation
Macaca
Viral Load
Interleukin-1
Mitogens
Chemokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

HIV-1 tat-mediated induction of platelet-derived growth factor in astrocytes : Role of early growth response gene 1. / Bethel-Brown, Crystal; Yao, Honghong; Callen, Shannon; Lee, Young Han; Dash, Prasanta K.; Kumar, Anil; Buch, Shilpa J.

In: Journal of Immunology, Vol. 186, No. 7, 01.04.2011, p. 4119-4129.

Research output: Contribution to journalArticle

Bethel-Brown, Crystal ; Yao, Honghong ; Callen, Shannon ; Lee, Young Han ; Dash, Prasanta K. ; Kumar, Anil ; Buch, Shilpa J. / HIV-1 tat-mediated induction of platelet-derived growth factor in astrocytes : Role of early growth response gene 1. In: Journal of Immunology. 2011 ; Vol. 186, No. 7. pp. 4119-4129.
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