Regulation of IL-8RA (CXCR1) expression in polymorphonuclear leukocytes by hypoxia/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 signals. 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 purpose of this study was to determine the effects of hypoxia and/or H/R 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 significant reduction in mRNA expression between 30 and 60 min. IL-8RA protein also decreased with reoxygenation of whole blood, which was altered by the addition of specific antioxidants. Therefore, H/R appears to attenuate the effect 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 inflammatory cytokines, but also control their actions by regulating their receptors.