A self-defence mechanism of astrocytes against Fas-mediated death involving interleukin-8 and CXCR2

Astrocytes play multiple roles from passive support to the regulation of inflammation during brain injury. This latter function is in part achieved by responses induced by the triggering of Fas expressed on astrocytes both in vitro and in vivo. It was previously shown that astrocytes are resistant to Fas-mediated death, responding to Fas triggering by interleukin-8 production. However, the cellular mechanisms by which astrocytes protect themselves from Fas-mediated death are unclear. Here, we show that survival of cultured astrocytes after Fas triggering is governed by the interaction of interleukin-8 with one of its receptors, CXCR2. Furthermore, interleukin-8 secretion and CXCR2 expression are both induced in human astrocytes after Fas stimulation, suggesting a new mechanism of self-defence against Fas-mediated death.