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The effects of these cytokines are mediated by cell surface receptors through a nuclear factor (NF)\u2010\u03baB\u2010dependent pathway that we have showed to be activated by UCB. The present study was designed to evaluate the role of TNF\u2010\u03b1 and IL\u20101\u03b2 signaling on astrocyte reactivity to UCB in rat cortical astrocytes. Exposure of astrocytes to UCB increased the expression of both TNF\u2010\u03b1 receptor (TNFR)1 and IL\u20101\u03b2 receptor (IL\u20101R)1, but not TNFR2, as well as their activation, observed by augmented binding of receptors' molecular adaptors, TRAF2 and TRAF6, respectively. Silencing of TNFR1, using siRNA technology, or blockade of IL\u20101\u03b2 cascade, using its endogenous antagonist, IL\u20101 receptor antagonist (IL\u20101ra), prevented UCB\u2010induced cytokine release and NF\u2010\u03baB activation. Interestingly, lack of TNF\u2010\u03b1 signal transduction reduced UCB\u2010induced cell death for short periods of incubation, although an increase was observed after extended exposure; in contrast, inhibition of IL\u20101\u03b2 cascade produced a sustained blockade of astrocyte injury by UCB. Together, our data show that inflammatory pathways are activated during<jats:italic>in vitro<\/jats:italic>exposure of rat cortical astrocytes to UCB and that this activation is prolonged in time. This supports the concept that inflammatory pathways play a role in brain damage by UCB, and that they may represent important pharmacological targets. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.21072","type":"journal-article","created":{"date-parts":[[2010,10,21]],"date-time":"2010-10-21T21:36:22Z","timestamp":1287696982000},"page":"14-25","source":"Crossref","is-referenced-by-count":30,"title":["Astrocyte reactivity to unconjugated bilirubin requires TNF\u2010\u03b1 and IL\u20101\u03b2 receptor signaling pathways"],"prefix":"10.1002","volume":"59","author":[{"given":"Adelaide","family":"Fernandes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreia","family":"Barateiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana 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