{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:22:01Z","timestamp":1790238121135,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2009,4,13]],"date-time":"2009-04-13T00:00:00Z","timestamp":1239580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Reactive astrogliosis is a key pathological aspect of neuroinflammatory disorders including human immunodeficiency virus type 1 (HIV\u20101)\u2010associated neurological disease. On the basis of previous data that showedastrocytes activated with interleukin (IL)\u20101\u03b2 induce neuronal injury, we analyzed global gene changes in IL\u20101\u03b2\u2010activated human astrocytes by gene microarray. Among the up\u2010regulated genes, CD38, a 45\u2010kDa type II single chain transmembrane glycoprotein, was a top candidate, with a 17.24\u2010fold change that was validated by real\u2010time polymerase chain reaction. Key functions of CD38 include enzymatic activities and involvement in adhesion and cell signaling. Importantly, CD38<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> T\u2010cell expression is a clinical correlate for progression of HIV\u20101 infection and biological marker for immune activation. Thus, CD38 expression in HIV\u20101 and\/or IL\u20101\u03b2\u2010stimulated human astrocytes and human brain tissues was analyzed. IL\u20101\u03b2 and HIV\u20101 activation of astrocytes enhanced CD38 mRNA levels. Both CD38 immunoreactivity and adenosine 5\u2032\u2010diphosphate (ADP)\u2010ribosyl cyclase activity were up\u2010regulated in IL\u20101\u03b2\u2010activated astrocytes. CD38 knockdown using specific siRNAs significantly reduced astrocyte proinflammatory cytokine and chemokine production. However, CD38 mRNA levels were unchanged in IL\u20101\u03b2 knockdown conditions, suggesting that IL\u20101\u03b2 autocrine loop is not implicated in this process. Quantitative immunohistochemical analysis of HIV\u2010seropositive without encephalitis and HIV\u20101 encephalitis brain tissues showed significant up\u2010regulation of CD38, which colocalized with glial fibrillary acidic protein\u2013positive 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\u20101 encephalitis. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22060","type":"journal-article","created":{"date-parts":[[2009,4,13]],"date-time":"2009-04-13T19:07:12Z","timestamp":1239649632000},"page":"2326-2339","source":"Crossref","is-referenced-by-count":52,"title":["CD38 regulation in activated astrocytes: Implications for neuroinflammation and HIV\u20101 brain 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