title: Air pollution-related metals induce differential cytokine responses in bronchial epithelial cells.
abstract: Different transition metals have been shown to induce inflammatory responses in lung. We have compared eight different metal ions with regard to cytokine responses, cytotoxicity and signalling mechanisms in a human lung epithelial cell model (BEAS-2B). Among the metal ions tested, there were large differences with respect to pro-inflammatory potential. Exposure to Cd(2+), Zn(2+) and As(3+) induced CXCL8 and IL-6 release at concentrations below 100μM, and Mn(2+) and Ni(2+) at concentrations above 200μM. In contrast, VO4(3-), Cu(2+) and Fe(2+) did not induce any significant increase of these cytokines. An expression array of 20 inflammatory relevant genes also showed a marked up-regulation of CXCL10, IL-10, IL-13 and CSF2 by one or more of the metal ions. The most potent metals, Cd(2+), Zn(2+) and As(3+) induced highest levels of oxidative activity, and ROS appeared to be central in their CXCL8 and IL-6 responses. Activation of the MAPK p38 seemed to be a critical mediator. However, the NF-κB pathway appeared predominately to be involved only in Zn(2+)- and As(3+)-induced CXCL8 and IL-6 responses. Thus, the most potent metals Cd(2+), Zn(2+) and As(3+) seemed to induce a similar pattern for the cytokine responses, and with some exceptions, via similar signalling mechanisms.
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, N-0403 Oslo, Norway. Electronic address: marit.lag@fhi.no.
authors.forename: M
authors.initials: M
authors.lastname: Låg
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, N-0403 Oslo, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Øvrevik
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, N-0403 Oslo, Norway.
authors.forename: A I
authors.initials: AI
authors.lastname: Totlandsdal
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, N-0403 Oslo, Norway.
authors.forename: E M
authors.initials: EM
authors.lastname: Lilleaas
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, N-0403 Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Thormodsæter
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, N-0403 Oslo, Norway.
authors.forename: J A
authors.initials: JA
authors.lastname: Holme
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, N-0403 Oslo, Norway.
authors.forename: P E
authors.initials: PE
authors.lastname: Schwarze
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, N-0403 Oslo, Norway.
authors.forename: M
authors.initials: M
authors.lastname: Refsnes
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution / Q000009:adverse effects; D001151:Arsenic / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D000074623:Dual Oxidases; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008670:Metals / Q000633:toxicity*; D019255:NADPH Oxidases / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D008670:Metals; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431513:DUOX1 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D001151:Arsenic
keywords: Cytokines; Epithelial lung cells; MAPK; Metals; NF-κB; Oxidative stress