title: 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.
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.
authors.affiliation: Department of Cell Biology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Jerel
authors.initials: J
authors.lastname: Fields
authors.forename: Jessica
authors.initials: J
authors.lastname: Gardner-Mercer
authors.forename: Kathleen
authors.initials: K
authors.lastname: Borgmann
authors.forename: Ian
authors.initials: I
authors.lastname: Clark
authors.forename: Anuja
authors.initials: A
authors.lastname: Ghorpade
mesh_terms: D000704:Analysis of Variance; D001253:Astrocytes / Q000378:metabolism* / Q000821:virology; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005333:Fetus; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D005904:Glial Fibrillary Acidic Protein; D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D013844:Thiazoles; D019715:Tissue Inhibitor of Metalloproteinase-1; C022616:thiazolyl blue