AhR- and c-maf-dependent induction of β7-integrin expression in human macrophages in response to environmental polycyclic aromatic hydrocarbons

In order to identify molecular targets of environmental polycyclic aromatic hydrocarbons (PAHs), we have analysed regulation of integrin (ITG) expression in PAH-exposed human macrophages. Among ITG subunits, β7 ITG was found to be markedly up-regulated at both mRNA and protein levels in response to the prototypical PAH benzo(a)pyrene (BP). Knock-down of the transcription factor c-maf, known to control β7 ITG expression, markedly impaired BP-mediated β7 ITG induction. Moreover, chromatin immunoprecipitation and electrophoretic mobility shift assays showed BP-triggered binding of c-maf to a specific maf-responsive element found in β7 ITG promoter. Such a binding, and also β7 ITG induction, were however abolished in response to chemical inhibition of the aryl hydrocarbon receptor (AhR), to which PAHs bind. Taken together, these data establish β7 ITG as a new molecular target of PAHs, whose up-regulation by these environmental contaminants most likely requires activation of co-operative pathways involving both AhR and c-maf.