Aryl hydrocarbon receptor-dependent induction of the IgA receptor FcαRI by the environmental contaminant benzo(a)pyrene in human macrophages

Autor: Sophie Desmots, Olivier Fardel, Lydie Sparfel, Laetitia Louarn, Marie-Laure Pinel-Marie
Přispěvatelé: Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National de l'Environnement Industriel et des Risques (INERIS), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UR), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Male
Macrophage
Receptors
Fc
MESH: Rats
Sprague-Dawley
Toxicology
Rats
Sprague-Dawley
chemistry.chemical_compound
0302 clinical medicine
Gene expression
polycyclic compounds
MESH: Animals
Nuclear protein
Receptor
MESH: Antigens
CD
Cells
Cultured
Aryl hydrocarbon receptor
0303 health sciences
biology
Benzo(a)pyrene
MESH: Environmental Pollutants
[SDV.TOX]Life Sciences [q-bio]/Toxicology
Environmental Pollutants
Tumor necrosis factor alpha
MESH: Receptors
Fc
MESH: Cells
Cultured
animal structures
MESH: Cell Line
Tumor
MESH: Rats
FcαRI/CD89
03 medical and health sciences
MESH: Benzo(a)pyrene
Antigens
CD
Cell Line
Tumor
Animals
Humans
Electrophoretic mobility shift assay
030304 developmental biology
Messenger RNA
MESH: Humans
Macrophages
MESH: Macrophages
Molecular biology
MESH: Male
Rats
Receptors
Aryl Hydrocarbon
chemistry
MESH: Receptors
Aryl Hydrocarbon
biology.protein
030215 immunology
Zdroj: Toxicology
Toxicology, Elsevier, 2011, 290 (1), pp.89-95. ⟨10.1016/j.tox.2011.08.018⟩
Toxicology, 2011, 290 (1), pp.89-95. ⟨10.1016/j.tox.2011.08.018⟩
ISSN: 0300-483X
DOI: 10.1016/j.tox.2011.08.018⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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