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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
Author(s) -
Fields Jerel,
GardnerMercer Jessica,
Borgmann Kathleen,
Clark Ian,
Ghorpade Anuja
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07203.x
Subject(s) - neuroinflammation , ccaat enhancer binding proteins , astrocyte , biology , microglia , gene knockdown , gene isoform , messenger rna , microbiology and biotechnology , immunology , transcription factor , endocrinology , inflammation , central nervous system , cell culture , dna binding protein , biochemistry , genetics , gene
J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07203.x 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.