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 Cd2+, Zn2+ and As3+ induced CXCL8 and IL-6 release at concentrations below 100μM, and Mn2+ and Ni2+ at concentrations above 200μM. In contrast, VO43−, Cu2+ and Fe2+ 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, Cd2+, Zn2+ and As3+ 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 Zn2+- and As3+-induced CXCL8 and IL-6 responses. Thus, the most potent metals Cd2+, Zn2+ and As3+ seemed to induce a similar pattern for the cytokine responses, and with some exceptions, via similar signalling mechanisms.