© 2002 American Thoracic Society DOI: 10.1165/rcmb.4821 Role of Bioavailable Iron in Coal Dust-Induced Activation of Activator Protein-1 and Nuclear Factor of Activated T CellsDifference between Pennsylvania and Utah Coal DustsDepartment of Environmental Medicine, New York University School of Medicine, New York, New York Address correspondence to: Xi Huang, Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, PHL Room 802, New York, NY 10016. Email: xihuang{at}env.med.nyu.edu Activator protein-1 (AP-1) and nuclear factor of activated T cells (NFAT) are two important transcription factors responsible for the regulation of cytokines, which are involved in cell proliferation and inflammation. Coal workers' pneumoconiosis (CWP) is an occupational lung disease that may be related to chronic inflammation caused by coal dust exposure. In the present study, we demonstrate that coal from the Pennsylvania (PA) coalmine region, which has a high prevalence of CWP, can activate both AP-1 and NFAT in JB6 mouse epidermal cells. In contrast, coal from the Utah (UT) coalmine region, which has a low prevalence of CWP, has no such effects. The PA coal stimulates mitogen-activated protein kinase (MAPK) family members of extracellular signal-regulated kinases (ERKs) and p38 MAPK but not c-Jun-NH2-terminal kinases, as determined by the phosphorylation assay. The increase in AP-1 by the PA coal was completely eliminated by the pretreatment of cells with PD98059, a specific MAPK kinase inhibitor, and SB202190, a p38 kinase inhibitor, further confirming that the PA coal-induced AP-1 activation is mediated through ERKs and p38 MAPK pathways. Deferoxamine (DFO), an iron chelator, synergistically enhanced the PA coal-induced AP-1 activity, but inhibited NFAT activity. For comparison, cells were treated with ferrous sulfate and/or DFO. We have found that iron transactivated both AP-1 and NFAT, and DFO further enhanced iron-induced AP-1 activation but inhibited NFAT. These results indicate that activation of AP-1 and NFAT by the PA coal is through bioavailable iron present in the coal. These data are in agreement with our previous findings that the prevalence of CWP correlates well with levels of bioavailable iron in coals from various mining regions.
Abbreviations: Activator protein-1, AP-1 • bioavailable iron, BAI • coal workers' pneumoconiosis, CWP • deferoxamine, DFO • extracellular signal-regulated kinases, ERK • fetal bovine serum, FBS • granulocyte macrophage-colony stimulating factor, GM-CSF • interleukin, IL • c-Jun-NH2-terminal kinase, JNK • mitogen-activated protein kinase, MAPK • minimal essential medium, MEM • nuclear factor of activated T cells, NFAT This article has been cited by other articles:
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