title: Aryl hydrocarbon receptor-dependent induction of the IgA receptor FcαRI by the environmental contaminant benzo(a)pyrene in human macrophages.
abstract: Polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (BaP), are widely distributed toxic environmental contaminants well known to regulate gene expression through activation of the aryl hydrocarbon receptor (AhR). In the present study, we demonstrated that the IgA receptor FcαRI/CD89 constitutes a molecular target for PAHs. Indeed, in vitro exposure to BaP markedly increased mRNA and protein expression of FcαRI in primary human macrophages; intratracheal instillation of BaP to rats also enhanced mRNA expression of FcαRI in alveolar macrophages. BaP concomitantly increased activity of the previously uncharacterized -1734 to -42 fragment of the FcaRI promoter that we subcloned in a luciferase reporter vector. Three-methylcholanthrene, a PAH known to activate AhR like BaP, induced FcαRI expression, in contrast to benzo(e)pyrene, a PAH known to poorly interact with AhR. Moreover, FcαRI induction in BaP-exposed human macrophages was fully prevented by down-regulating AhR expression through small interference RNA transfection. In addition, BaP increased nuclear protein binding to a consensus AhR-related xenobiotic-responsive element found in the FcαRI gene promoter, as revealed by electrophoretic mobility shift assay. Overall, these data highlight an AhR-dependent up-regulation of FcαRI in response to BaP, which may contribute to the deleterious effects of environmental PAHs toward the immune/inflammatory response and which also likely emphasizes the role played by AhR in the regulation of genes involved in immunity and inflammation.
authors.affiliation: Institut de Recherche sur la Santé, l'Environnement et le Travail (IRSET), EA-4427 Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes, France. marie-laure.pinel@univ-rennes1.fr
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Pinel-Marie
authors.forename: Laetitia
authors.initials: L
authors.lastname: Louarn
authors.forename: Sophie
authors.initials: S
authors.lastname: Desmots
authors.forename: Olivier
authors.initials: O
authors.lastname: Fardel
authors.forename: Lydie
authors.initials: L
authors.lastname: Sparfel
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis*; D011961:Receptors, Fc / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; D004785:Environmental Pollutants; C036832:Fc(alpha) receptor; C045281:IgA receptor; D018336:Receptors, Aryl Hydrocarbon; D011961:Receptors, Fc; D001564:Benzo(a)pyrene