TY - JOUR
T1 - CD38 regulation in activated astrocytes
T2 - Implications for neuroinflammation and HIV-1 brain infection
AU - Kou, Wei
AU - Banerjee, Sugato
AU - Eudy, James
AU - Smith, Lynette M.
AU - Persidsky, Raisa
AU - Borgmann, Kathleen
AU - Wu, Li
AU - Sakhuja, Namita
AU - Deshpande, Muralidhar S.
AU - Walseth, Timothy F.
AU - Ghorpade, Anuja
PY - 2009/8/1
Y1 - 2009/8/1
N2 - Reactive astrogliosis is a key pathological aspect of neuroinflammatory disorders including human immunodeficiency virus type 1 (HIV-1)-associated neurological disease. On the basis of previous data that showed astrocytes activated with interleukin (IL)-1b induce neuronal injury, we analyzed global gene changes in IL-1b-activated human astrocytes by gene microarray. Among the up-regulated genes, CD38, a 45- kDa type II single chain transmembrane glycoprotein, was a top candidate, with a 17.24-fold change that was validated by real-time polymerase chain reaction. Key functions of CD38 include enzymatic activities and involvement in adhesion and cell signaling. Importantly, CD38+CD8+ T-cell expression is a clinical correlate for progression of HIV-1 infection and biological marker for immune activation. Thus, CD38 expression in HIV-1 and/or IL-1β-stimulated human astrocytes and human brain tissues was analyzed. IL-1β and HIV-1 activation of astrocytes enhanced CD38 mRNA levels. Both CD38 immunoreactivity and adenosine 5′-diphosphate (ADP)- ribosyl cyclase activity were up-regulated in IL-1β-activated astrocytes. CD38 knockdown using specific siRNAs significantly reduced astrocyte proinflammatory cytokine and chemokine production. However, CD38 mRNA levels were unchanged in IL-1β knockdown conditions, suggesting that IL-1b autocrine loop is not implicated in this process. Quantitative immunohistochemical analysis of HIV-seropositive without encephalitis and HIV-1 encephalitis brain tissues showed significant upregulation of CD38, which colocalized with glial fibrillary acidic protein-positive cells in areas of inflammation. These results suggest an important role of CD38 in the regulation of astrocyte dysfunction during the neuroinflammatory processes involved in neurodegenerative/neuroinflammatory disorders such as HIV-1 encephalitis.
AB - Reactive astrogliosis is a key pathological aspect of neuroinflammatory disorders including human immunodeficiency virus type 1 (HIV-1)-associated neurological disease. On the basis of previous data that showed astrocytes activated with interleukin (IL)-1b induce neuronal injury, we analyzed global gene changes in IL-1b-activated human astrocytes by gene microarray. Among the up-regulated genes, CD38, a 45- kDa type II single chain transmembrane glycoprotein, was a top candidate, with a 17.24-fold change that was validated by real-time polymerase chain reaction. Key functions of CD38 include enzymatic activities and involvement in adhesion and cell signaling. Importantly, CD38+CD8+ T-cell expression is a clinical correlate for progression of HIV-1 infection and biological marker for immune activation. Thus, CD38 expression in HIV-1 and/or IL-1β-stimulated human astrocytes and human brain tissues was analyzed. IL-1β and HIV-1 activation of astrocytes enhanced CD38 mRNA levels. Both CD38 immunoreactivity and adenosine 5′-diphosphate (ADP)- ribosyl cyclase activity were up-regulated in IL-1β-activated astrocytes. CD38 knockdown using specific siRNAs significantly reduced astrocyte proinflammatory cytokine and chemokine production. However, CD38 mRNA levels were unchanged in IL-1β knockdown conditions, suggesting that IL-1b autocrine loop is not implicated in this process. Quantitative immunohistochemical analysis of HIV-seropositive without encephalitis and HIV-1 encephalitis brain tissues showed significant upregulation of CD38, which colocalized with glial fibrillary acidic protein-positive cells in areas of inflammation. These results suggest an important role of CD38 in the regulation of astrocyte dysfunction during the neuroinflammatory processes involved in neurodegenerative/neuroinflammatory disorders such as HIV-1 encephalitis.
KW - Astrocyte activation
KW - Glial inflammation
KW - HIV-1-associated dementia
KW - IL-1β
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U2 - 10.1002/jnr.22060
DO - 10.1002/jnr.22060
M3 - Article
C2 - 19365854
AN - SCOPUS:69249231115
SN - 0360-4012
VL - 87
SP - 2326
EP - 2339
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 10
ER -