Crocidolite activates NF-kappa B and MIP-2 gene expression in rat alveolar epithelial cells. Role of mitochondrial-derived oxidants.
Nuclear factor kappa B (NF-kappa B) is a transcription factor that regulates expression of several genes coding for inflammatory and immunoregulatory proteins including the neutrophil chemotactic cytokine MIP-2. In previous studies we found that crocidolite asbestos activates the nuclear translocation of NF-kappa B as well as MIP-2 gene expression in rat alveolar type II cells. Here we report that both crocidolite-induced NF-kappa B activation of MIP-2 gene expression can be attenuated by the antioxidant tetramethylthiourea, suggesting the dependence of these responses on oxidative stress. Crocidolite exposure of RLE-TN cells also increased production of H2O2, a response that was inhibited by the mitochondrial respiratory chain inhibitor thenoyltrifluoroacetone (TTFA). TTFA treatment of RLE-6TN cells also inhibited crocidolite-induced nuclear translocation of NF-kappa B and MIP-2 gene expression. These results indicate crocidolite exposure of rat alveolar type II cells results in increased production of mitochondrial-derived hydrogen peroxide and that mitochondrial-derived oxidants contribute to crocidolite activation of NF-kappa B and increases in MIP-2 gene expression.
Driscoll
K E
KE
Procter & Gamble Pharmaceuticals, Health Care Research Center, Cincinnati, OH 45040-8006, USA. driscollke@pg.com
Carter
J M
JM
Howard
B W
BW
Hassenbein
D
D
Janssen
Y M
YM
Mossman
B T
BT
D000818:Animals; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D001483:Base Sequence; D002460:Cell Line; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D013481:Superoxides / Q000378:metabolism
D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D017931:DNA Primers; D016328:NF-kappa B; D013481:Superoxides; D017638:Asbestos, Crocidolite; D006861:Hydrogen Peroxide