Biochemical and Biophysical Research Communications, Vol.358, No.2, 442-448, 2007
AhR- and c-maf-dependent induction of beta 7-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, beta 7 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 beta 7 ITG expression, markedly impaired BP-mediated beta 7 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 beta 7 ITG promoter. Such a binding, and also beta 7 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 beta 7 ITG as a new molecular target of PAHs, whose upregulation by these environmental contaminants most likely requires activation of co-operative pathways involving both AhR and c-maf. (C) 2007 Elsevier Inc. All rights reserved.