CD38 regulation in activated astrocytes

Implications for neuroinflammation and HIV-1 brain infection

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

Research output: Contribution to journalArticle

27 Citations (Scopus)

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

Fingerprint

Astrocytes
HIV-1
Interleukin-1
Brain
Infection
Interleukins
Encephalitis
Genes
Virus Activation
Messenger RNA
Glial Fibrillary Acidic Protein
Virus Diseases
Chemokines
Cell Adhesion
Neurodegenerative Diseases
Adenosine Diphosphate
Real-Time Polymerase Chain Reaction
Glycoproteins
Up-Regulation
Biomarkers

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

CD38 regulation in activated astrocytes : Implications for neuroinflammation and HIV-1 brain infection. / Kou, Wei; Banerjee, Sugato; Eudy, James D; Smith, Lynette M; Persidsky, Raisa; Borgmann, Kathleen; Wu, Li; Sakhuja, Namita; Deshpande, Muralidhar S.; Walseth, Timothy F.; Ghorpade, Anuja.

In: Journal of Neuroscience Research, Vol. 87, No. 10, 01.08.2009, p. 2326-2339.

Research output: Contribution to journalArticle

Kou, W, Banerjee, S, Eudy, JD, Smith, LM, Persidsky, R, Borgmann, K, Wu, L, Sakhuja, N, Deshpande, MS, Walseth, TF & Ghorpade, A 2009, 'CD38 regulation in activated astrocytes: Implications for neuroinflammation and HIV-1 brain infection', Journal of Neuroscience Research, vol. 87, no. 10, pp. 2326-2339. https://doi.org/10.1002/jnr.22060
Kou, Wei ; Banerjee, Sugato ; Eudy, James D ; Smith, Lynette M ; Persidsky, Raisa ; Borgmann, Kathleen ; Wu, Li ; Sakhuja, Namita ; Deshpande, Muralidhar S. ; Walseth, Timothy F. ; Ghorpade, Anuja. / CD38 regulation in activated astrocytes : Implications for neuroinflammation and HIV-1 brain infection. In: Journal of Neuroscience Research. 2009 ; Vol. 87, No. 10. pp. 2326-2339.
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AU - Wu, Li

AU - Sakhuja, Namita

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AU - Walseth, Timothy F.

AU - Ghorpade, Anuja

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