title: Calcium signaling and β2-adrenergic receptors regulate 1-nitropyrene induced CXCL8 responses in BEAS-2B cells.
abstract: Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are widespread environmental pollutants, generated from reactions between PAHs and nitrogen oxides during combustion processes. In the present study we have investigated the mechanisms of CXCL8 (IL-8) responses induced by 1-nitropyrene (1-NP) in human bronchial epithelial BEAS-2B cells, with focus on the possible importance of Ca(2+)-signaling and activation of β2-adrenergic receptors (β2AR). Ca(2+)-chelator treatment obliterated 1-NP-induced CXCL8 (IL-8) responses. 1-NP at 10μM (but not 1μM) induced a rapid and sustained increase in intracellular Ca(2+)-levels ([Ca(2+)]i). The early but not the later, sustained phase of 1-NP-induced [Ca(2+)]i was suppressed by beta-blocker treatment (carazolol). Moreover, inhibition of β2AR by blocking-antibody, beta-blocker treatment (ICI 118551) or siRNA transfection attenuated CXCL8 responses induced by 1-NP. The results confirm that PAHs may induce Ca(2+)-signaling also in BEAS-2B cells, at least partly through activation of β2AR, and suggest that both β2AR- and Ca(2+)-signaling may be involved in 1-NP-induced CXCL8 responses in bronchial epithelial cells.
authors.affiliation: UMR Inserm 1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France; Université de Rennes 1, SFR BIOSIT, Faculté des Sciences Pharmaceutiques et Biologiques, Rennes, France.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Mayati
authors.affiliation: UMR Inserm 1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France; Université de Rennes 1, SFR BIOSIT, Faculté des Sciences Pharmaceutiques et Biologiques, Rennes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Le Ferrec
authors.affiliation: Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Jørn A
authors.initials: JA
authors.lastname: Holme
authors.affiliation: UMR Inserm 1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France; Université de Rennes 1, SFR BIOSIT, Faculté des Sciences Pharmaceutiques et Biologiques, Rennes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fardel
authors.affiliation: UMR Inserm 1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France; Université de Rennes 1, SFR BIOSIT, Faculté des Sciences Pharmaceutiques et Biologiques, Rennes, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Lagadic-Gossmann
authors.affiliation: Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway. Electronic address: johan.ovrevik@fhi.no.
authors.forename: Johan
authors.initials: J
authors.lastname: Ovrevik
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D011721:Pyrenes / Q000633:toxicity*; D034741:RNA, Small Interfering / Q000008:administration & dosage; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D011721:Pyrenes; D034741:RNA, Small Interfering; D018343:Receptors, Adrenergic, beta-2; D002118:Calcium; C032668:1-nitropyrene
keywords: Adrenergic receptors; Calcium; Chemokines; Inflammation; Lung; Polycyclic aromatic hydrocarbons