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

TitleCCAAT/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
Publication TypeJournal Article
Year of Publication2011
AuthorsFields, J, Gardner-Mercer, J, Borgmann, K, Clark, I, Ghorpade, A
JournalJournal of Neurochemistry
Volume118
Issue1
Pagination93-104
Date Published07/2011
KeywordsAstrocyte, C/EBPβ, External, HIV-1-associated dementia, Neuroinflammation, TIMP-1
Abstract

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. In vitro, 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.

URLhttp://www.ncbi.nlm.nih.gov/pubmed/21281310
DOI10.1111/j.1471-4159.2011.07203.x