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

Fields, Jerel, Gardner-Mercer, Jessica, Borgmann, Kathleen, Clark, Ian M. and Ghorpade, Anuja (2011) 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. Journal of Neurochemistry, 118. pp. 93-104. ISSN 1471-4159

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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 ß (C/EBPß), 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/EBPß 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/EBPß nuclear expression in human astrocytes through 7 days of treatment. Over-expression of C/EBPß increases TIMP-1 promoter activity, mRNA, and protein levels in human astrocytes activated with interleukin-1ß. Knockdown of C/EBPß with siRNA decreases TIMP-1 mRNA and protein levels. These data suggest that C/EBPß 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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: Users 2731 not found.
Date Deposited: 13 May 2011 11:12
Last Modified: 21 Jul 2020 23:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/30537
DOI: 10.1111/j.1471-4159.2011.07203.x

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