Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Iron-induced interleukin-6 gene expression: possible mediation through the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways.

Authors
Dai-J; Huang-C; Wu-J; Yang-C; Frenkel-K; Huang-X
Source
Toxicology 2004 Oct; 203(1-3):199-209
NIOSHTIC No.
20029043
Abstract
Increased iron store in the body may increase the risk of many diseases such as cancer and inflammation. However, the precise pathogenic mechanism of iron has not yet been elucidated. In the present study, the early biological responses of cells to iron treatment were investigated in AP-1 luciferase reporter stably transfected mouse epidermal JB6 cells and primary rat hepatocytes. It was shown that water-soluble iron compounds, such as FeSO4 and Fe2(SO4)3, were more active in inducing AP-1 in JB6 cells than water-insoluble iron compounds, such as Fe2O3 and FeS. Iron stimulated mitogen-activated protein kinase (MAPK) family members of extracellular signal-regulated kinases (ERKs) and p38 MAPK but not c-jun NH2 terminal kinases (JNKs), both in JB6 cells and in primary rat hepatocytes, as determined by the phosphorylation assay. Interestingly, the increase in AP-1 luciferase activity by iron was inhibited by the pretreatment of the cells with PD98059, a specific MEK1 inhibitor, and SB202190, a p38 kinase inhibitor. Levels of interleukin-6 (IL-6), a pro-inflammatory cytokine, were increased in JB6 cells by iron in a dose-dependent manner. The increase in IL-6 and its mRNA by iron was also eliminated by the pretreatment of the cells with PD98059 and SB202190. Since the IL-6 promoter contains an AP-1 binding site, our studies indicate that the iron-induced IL-6 gene expression may be mediated through ERKs and p38 MAPK pathways, possibly one of the important mechanisms for the pathogenesis of iron overload.
Keywords
Iron-compounds; Calcium-compounds; Injuries; Coal-miners; Coal-mining; Health-hazards; Pneumoconiosis; Coal-dust; Cell-damage; Lung-cells; Lung-disease; Injury-prevention; Coal-workers-pneumoconiosis; Black-lung
Contact
Department of Environmental Medicine, NYU Cancer Institute, New York University School of Medicine, PHL Room 802, New York, NY 10016
CODEN
TXCYAC
CAS No.
7439-89-6; 7440-70-2; 471-34-1
Publication Date
20041015
Document Type
Journal Article
Funding Amount
638746
Funding Type
Grant
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-003561
Issue of Publication
1-3
ISSN
0300-483X
Source Name
Toxicology
State
NY
Performing Organization
New York University Medical Center, New York, New York
TOP