Activation of p38 MAP Kinase by Crocidolite in Mesothelial Cells is Dependent Upon Oxidative Stress

Abstract

Activation of extracellular-regulated mitogen-activated protein kinase by asbestos in mesothelial cells has been well documented. However, investigations into the p38 pathway have not been undertaken until now. In our study we set out to investigate the mechanism of p38 activation and a possible role for it in asbestos-mediated cell injury. A rat mesothelial cell line (4/4 RM-4) was treated with crocidolite asbestos at a range of doses and time points with or without antioxidants. Western blotting and in vitro complex kinase assays showed that crocidolite increased both p38 phosphorylation and activation in a time- and dose-dependent manner, and that these increases could be reduced by preincubating cells with antioxidants. Additionally, SB203580, a specific inhibitor of the p38 pathway, reduced crocidolite-induced activator protein DNA binding as shown by gel mobility shift assay.