Benzo(a)pyrene (BP) is an environmental contaminant known to favor airway 
inflammation likely through up-regulation of pro-inflammatory cytokines. The 
present study was designed to characterize its effects toward interleukin-8 
(IL-8), a well-established pulmonary inflammatory cytokine. In primary human 
macrophages, BP was shown to induce IL-8 expression at both mRNA and secretion 
levels in a dose-dependent manner. Such an up-regulation was likely linked to 
aryl hydrocarbon receptor (AhR)-activation since BP-mediated IL-8 induction was 
reduced after AhR expression knock-down through RNA interference. Moreover, 
electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation 
experiments showed BP-triggered binding of AhR to a consensus xenobiotic 
responsive element (XRE) found in the human IL-8 promoter. Finally, BP 
administration to mice led to over-expression of keratinocyte chemoattractant 
(KC), the murine functional homologue of IL-8, in lung. It also triggered the 
recruitment of neutrophils in bronchoalveolar lavage (BAL) fluids, which was 
however fully abolished in the presence of a chemical antagonist of the KC/IL-8 
receptors CXCR1/CXCR2, thus supporting the functional and crucial involvement of 
KC in BP-induced lung inflammation. Overall, these data highlight an 
AhR-dependent regulation of IL-8 in response to BP that likely contributes to 
the airway inflammatory effects of this environmental chemical.