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

Date Published:
07/2011

Publication Type:
Journal Article

Authors:

Secondary:
Journal of Neurochemistry

Volume:
118

Pagination:
93-104

Issue:
1

URL:
https://pubmed.ncbi.nlm.nih.gov/

DOI:
10.1111/j.1471-4159.2011.07203.x

Keywords:
Astrocyte;C/EBPβ;External;HIV-1-associated dementia;Neuroinflammation;TIMP-1

Abstract:
<p>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/EBP), a transcription factor, is detected in rodent brains in response to neuroinflammation, implicating it in Alzheimer’s, Parkinson’s and HIV-1-associated neurocognitive disorders (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. <em>In vitro</em>, HAND-relevant stimuli synergistically induce C/EBPβ nuclear expression in human astrocytes through 7 days of stimulations. Overexpression of C/EBPβ increases TIMP-1 promoter activity, mRNA and protein levels in human astrocytes activated with IL-1β. Knockdown of C/EBPβ with siRNA decreases TIMP-1 mRNA and protein levels. These data suggest 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.</p>