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Zinc- and Copper-Induced Interleukin-6 Release in Primary Cell Cultures From Rat Heart

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Abstract

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 μM)-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.

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Acknowledgments

We thank Tonje Skuland for helping to prepare the figures and Annike I. Totlandsdal for feedback on the manuscript. This work was supported by the Research Council of Norway.

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  1. V. Ansteinsson

    Present address: Nordic Institute of Dental Materials (NIOM), Haslum, Norway

Authors and Affiliations

  1. Division of Environmental Medicine, Norwegian Institute of Public Health, Nydalen, P.O. Box 4404, 0403, Oslo, Norway

    V. Ansteinsson, M. Refsnes & M. Låg

  2. Department of Pharmacology, UiO, P.O. Box 1057, Blindern, 0316, Oslo, Norway

    T. Skomedal, J. B. Osnes & I. Schiander

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  1. V. Ansteinsson
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Ansteinsson, V., Refsnes, M., Skomedal, T. et al. Zinc- and Copper-Induced Interleukin-6 Release in Primary Cell Cultures From Rat Heart. Cardiovasc Toxicol 9, 86–94 (2009). https://doi.org/10.1007/s12012-009-9043-5

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