CCAAT/enhancer binding protein β expression is increased in the brain during HIV-1-infection and contributes to regulation of astrocyte tissue inhibitor of metalloproteinase-1

Jerel Fields, Jessica Gardner-Mercer, Kathleen Borgmann, Ian Clark, Anuja Ghorpade

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND) associated with infection and activation of mononuclear phagocytes (MP) in the brain, occur late in disease. Infected/activated MP initiate neuroinflammation activating glial cells and ultimately disrupting neuronal function. Astrocytes secrete tissue inhibitor of metalloproteinase (TIMP)-1 in response to neural injury. Altered TIMP-1 levels are implicated in several CNS diseases. CCAAT enhancer-binding protein β (C/EBPβ), a transcription factor, is expressed in rodent brains in response to neuroinflammation, implicating it in Alzheimer's, Parkinson's, and HAND. Here, we report that C/EBPβ mRNA levels are elevated and its isoforms differentially expressed in total brain tissue lysates of HIV-1-infected and HIV-1 encephalitis patients. In vitro, HAND-relevant stimuli additively induce C/EBPβ nuclear expression in human astrocytes through 7 days of treatment. Over-expression of C/EBPβ increases TIMP-1 promoter activity, mRNA, and protein levels in human astrocytes activated with interleukin-1β. Knockdown of C/EBPβ with siRNA decreases TIMP-1 mRNA and protein levels. These data suggest that C/EBPβ isoforms are involved in complex regulation of astrocyte TIMP-1 production during HIV-1 infection; however, further studies are required to completely understand their role during disease progression.

Original languageEnglish
Pages (from-to)93-104
Number of pages12
JournalJournal of Neurochemistry
Volume118
Issue number1
DOIs
Publication statusPublished - 1 Jul 2011

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Keywords

  • CCAAT enhancer-binding protein β
  • astrocyte and neuroinflammation
  • human immunodeficiency virus-1-associated dementia
  • tissue inhibitor of metalloproteinase-1

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