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.
Ansteinsson
V
V
Division of Environmental Medicine, Norwegian Institute of Public Health, Nydalen, P.O. Box 4404, 0403 Oslo, Norway.
Refsnes
M
M
Skomedal
T
T
Osnes
J B
JB
Schiander
I
I
Låg
M
M
D000818:Animals; D002478:Cells, Cultured; D003300:Copper / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000633:toxicity*
D015850:Interleukin-6; D003300:Copper; D048049:Extracellular Signal-Regulated MAP Kinases; D015032:Zinc