CD38 regulation in activated astrocytes: Implications for neuroinflammation and HIV-1 brain infection

Wei Kou, Sugato Banerjee, James Eudy, Lynette M. Smith, Raisa Persidsky, Kathleen Borgmann, Li Wu, Namita Sakhuja, Muralidhar S. Deshpande, Timothy F. Walseth, Anuja Ghorpade

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29 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2326-2339
Number of pages14
JournalJournal of Neuroscience Research
Volume87
Issue number10
DOIs
StatePublished - 1 Aug 2009

Keywords

  • Astrocyte activation
  • Glial inflammation
  • HIV-1-associated dementia
  • IL-1β

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    Kou, W., Banerjee, S., Eudy, J., Smith, L. M., Persidsky, R., Borgmann, K., Wu, L., Sakhuja, N., Deshpande, M. S., Walseth, T. F., & Ghorpade, A. (2009). CD38 regulation in activated astrocytes: Implications for neuroinflammation and HIV-1 brain infection. Journal of Neuroscience Research, 87(10), 2326-2339. https://doi.org/10.1002/jnr.22060