TY - JOUR
T1 - 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
AU - Fields, Jerel
AU - Gardner-Mercer, Jessica
AU - Borgmann, Kathleen
AU - Clark, Ian
AU - Ghorpade, Anuja
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - CCAAT enhancer-binding protein β
KW - astrocyte and neuroinflammation
KW - human immunodeficiency virus-1-associated dementia
KW - tissue inhibitor of metalloproteinase-1
UR - http://www.scopus.com/inward/record.url?scp=79958825362&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2011.07203.x
DO - 10.1111/j.1471-4159.2011.07203.x
M3 - Article
C2 - 21281310
AN - SCOPUS:79958825362
SN - 0022-3042
VL - 118
SP - 93
EP - 104
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 1
ER -