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CD40 is a 50\u2010kDa protein on the surface of microglia, and we have previously shown that it is increased in expression in HIV\u20101\u2010infected brain tissue as well as by interferon\u2010\u03b3 (IFN\u03b3) in tissue culture. We examined the expression and regulation of CXCL8 in cultured human fetal microglia after ligation of CD40 with soluble trimeric CD40 ligand (sCD40L) as well as the expression of CXCL8 on microglia in HIV encephalitic brain tissue sections. Treatment of cultured microglia with IFN\u03b3 + sCD40L resulted in significant induction of CXCL8. This expression was mediated by activation of the ERK1\/2 MAPK pathway, as demonstrated by ELISA and Western blot using a specific inhibitor (U0126). Gel shift analyses demonstrated that NF\u03baB and AP\u20101, but not C\/EBP\u03b2, mediate microglial CXCL8 production. We also found increased colocalization of CXCL8 with CD68\/CD40\u2010positive cells in HIV encephalitic brain tissue compared with HIV\u2010infected nonencephalitic and normal tissue. Thus, CD40\u2010CD40L interactions facilitate chemokine expression, leading to the influx of inflammatory cells into the CNS. These events can lead to the pathology that is associated with neuroinflammatory diseases. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.21525","type":"journal-article","created":{"date-parts":[[2007,10,5]],"date-time":"2007-10-05T23:17:04Z","timestamp":1191626224000},"page":"630-639","source":"Crossref","is-referenced-by-count":32,"title":["CD40\u2010CD40 ligand interactions in human microglia induce CXCL8 (interleukin\u20108) secretion by a mechanism dependent on activation of ERK1\/2 and nuclear translocation of nuclear factor\u2010\u03baB (NF\u03baB) and activator protein\u20101 (AP\u20101)"],"prefix":"10.1002","volume":"86","author":[{"given":"Teresa G.","family":"D'Aversa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliseo A.","family":"Eugenin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan 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