Activation of MAP kinases by hexavalent chromium, manganese and nickel in human lung epithelial cells.
Epidemiological studies indicate that workers who perform welding operations are at increased risk for bronchitis, siderosis, occupational asthma and lung cancer due to fume exposure. Welding fumes are a complex chemical mixture, and the metal composition is hypothesized to be an etiological factor in respiratory disease due to this exposure. In the present study, human lung epithelial cells in vitro responded to hexavalent chromium, manganese and nickel over a concentration range of 0.2-200 microM with a significant increase in intracellular phosphoprotein (a measure of stress response pathway activation). The mitogen-activated protein kinases ERK1/2, SAPK/JNK and p38 were activated via phosphorylation following 1-h exposures. Hexavalent chromium up-regulated p-38 phosphorylation 23-fold and SAPK/JNK phosphorylation 17-fold, with a comparatively modest 4-fold increase in ERK1/2 phosphorylation. Manganese caused a two- to four-fold increase in SAPK/JNK and ERK 1/2 phosphorylation, with no observed effects on p38 kinase. Nickel caused increased (two-fold) phosphorylation of ERK 1/2 only, and was not cytotoxic over the tested concentration range. The observed effects of welding fume metals on cellular signaling in lung epithelium demonstrate a potentially significant interplay between stress-response signaling (p38 and SAPK/JNK) and anti-apototic signaling (ERK 1/2) that is dependant on the specific metal or combination of metals involved.
Tessier
Daniel M
DM
Division of Environmental & Occupational Health Sciences, School of Public Health, University of Illinois Chicago, SPH/EOHS/MC922, Chicago, IL 60612, USA. dmt@uic.edu
Pascal
Laura E
LE
D000395:Air Pollutants, Occupational; D002478:Cells, Cultured; D002857:Chromium / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000201:enzymology; D008345:Manganese / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009532:Nickel / Q000633:toxicity*; D016273:Occupational Exposure; D010766:Phosphorylation; D014896:Welding
D000395:Air Pollutants, Occupational; D002857:Chromium; C074702:chromium hexavalent ion; D008345:Manganese; D009532:Nickel; D020928:Mitogen-Activated Protein Kinases