Air pollution-related metals induce differential cytokine responses in bronchial epithelial cells

• Published in: Toxicology in vitro 2016-10, Vol.36, p.53-65
• Main Authors: Låg, M, Øvrevik, J, Totlandsdal, A I, Lilleaas, E M, Thormodsæter, A, Holme, J A, Schwarze, P E, Refsnes, M
• Format: Article
• Language: English
• Subjects: Air Pollutants - toxicity; Air Pollution - adverse effects; Arsenic - toxicity; Bronchi - cytology; Cell Line; Cell Survival - drug effects; Cytokines - genetics; Cytokines - metabolism; Dual Oxidases; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gene Expression Regulation - drug effects; Humans; Metals - toxicity; NADPH Oxidases - genetics; NF-kappa B - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Reactive Oxygen Species - metabolism; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; Transcription Factor RelA - genetics
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2016.07.004

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.