Regulation of IL-8RA (CXCR1) expression in polymorphonuclear leukocytes byhypoxia/reoxygenation

Interleukin-8 (IL-8) is an important mediator of neutrophil (PMN) function and the type A IL-8 receptor (IL-8RA) mediates these pro-inflammatory signa ls, Hypoxia or hypoxia/reoxygenation (H/R) affects the production of IL-8, but no data is available regarding its effect on IL-8RA expression. The pur pose of this study was to determine the effects of hypoxia and/or WR on the expression of IL-8RA in PMN, We demonstrated that IL-8RA mRNA levels were similar under normoxic and hypoxic conditions but H/R resulted in a signifi cant reduction in mRNA expression between 30 and 60 ruin, IL-8RA protein al so decreased with reoxygenation of whole blood, which was altered by the ad dition of specific antioxidants, Therefore, WR appears to attenuate the eff ect of IL-8 by down-regulating IL-8RA in PMN, These data show that changes in oxygen tension within the wound site not only affect the expression of i nflammatory cytokines, but also control their actions by regulating their r eceptors.