Zinc- and copper-induced interleukin-6 release in primary cell cultures from rat heart

The metals, zinc (Zn2+) and copper (Cu2+) from inhaled particulate matter may reach the systemic circulation and the cardiac tissue. In the present study, the potential of Zn2+ and Cu2+ to induce interleukin (IL)-6 responses in cardiomyocytes (CMs) and cardiac fibroblasts (CFs), in mono- and cocultures, was examined. Both metals induced IL-6 release in a concentration (20-200 microM)-dependent manner. Zn2+ appeared more potent than Cu2+ in both mono- and cocultures of CMs and CFs. In the cocultures, the basal- and metal-induced IL-6 responses were synergistically increased compared to the monocultures. Exposure to Zn2+ increased phosphorylation of the MAP-kinases, ERK1/2 and p38, in monocultures of CMs and CFs. Cu2+ induced an increased phosphorylation of p38 in both cell types and of ERK1/2 in CFs, but at higher concentrations than Zn2+. Treatment with a p38 inhibitor (SB202190) reduced the IL-6 responses to Zn2+ and Cu2+ in both cell types. Pretreatment with PD98059 to inhibit ERK1/2 was without significant effect; however, insignificant reductions was observed in the in the CFs. In conclusion, Zn2+ and Cu2+ increased IL-6 release and MAP-kinase activation in primary cardiac cells, processes known to be involved in cardiac inflammation and hypertrophy.