Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Gene Expression Analysis of Lung Injury in Rats Induced by Exposure to MMA-SS Welding Fume for 30 Days

  • Oh, Jung-Hwa (Toxicogenomics Team, Korea Institute of Toxicology) ;
  • Park, Han-Jin (Toxicogenomics Team, Korea Institute of Toxicology) ;
  • Heo, Sun-Hee (Toxicogenomics Team, Korea Institute of Toxicology) ;
  • Yang, Mi-Jin (Inhalation toxicology Team, Korea Institute of Toxicology) ;
  • Yang, Young-Su (Inhalation toxicology Team, Korea Institute of Toxicology) ;
  • Song, Chang-Woo (Inhalation toxicology Team, Korea Institute of Toxicology) ;
  • Yoon, Seok-Joo (Toxicogenomics Team, Korea Institute of Toxicology)
  • Published : 2007.12.31
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Abstract

The welding fume has been implicated as a causal agent in respiratory disease such as pneumoconiosis. The molecular mechanism by which welding fume induces toxicity in the lung is still unknown, but studies have focused on histological structure and indirect approach measuring the pulmonary damage markers. In the present study, gene expression profiles were analyzed in the lung of rats exposed by manual metal-arc stainless-steel (MMA-SS) welding fume for 30 days using Affymetrix GeneChip$^{(R)}$. Totally, 379 genes were identified as being either up- or down-regulated over 2-fold changes (P<0.01) in the lung of low- or high-dose group and were analyzed by using hierarchical clustering. We focused on genes involved in immune/inflammation responses were differentially regulated during lung injury induced by welding fume exposure. The information of these deregulated genes may contribute in elucidation of the inflammation mechanism during lung injury such as lung fibrosis.

Keywords

References

  1. Morgan, W. K. C. On welding, wheezing, and whimsy. Am Ind Hyg Assoc J 50:59-69 (1989) https://doi.org/10.1080/15298668991374318
  2. Tuschl, H., Weber, E. & Kovac, R. Investigations on immune parameters in welders. J Appl Toxicol 17: 377-383 (1997) https://doi.org/10.1002/(SICI)1099-1263(199711/12)17:6<377::AID-JAT454>3.0.CO;2-8
  3. Yu, I. J. et al. Lung fibrosis in Sprague-Dawley rats, induced by exposure to manual metal arc-stainless steel welding fumes. Toxicol Sci 63:99-106 (2001) https://doi.org/10.1093/toxsci/63.1.99
  4. Yu, I. J. et al. Recovery from manual metal arc-stainless steel welding-fume exposure induced lung fibrosis in Sprague-Dawley rats. Toxicol Lett 143:247-259 (2003) https://doi.org/10.1016/S0378-4274(03)00154-1
  5. Yu, I. J. et al. Recovery from welding-fume-exposure-induced lung fibrosis and pulmonary function changes in sprague dawley rats. Toxicol Sci 82:608-613 (2004) https://doi.org/10.1093/toxsci/kfh289
  6. Hedenstedt, A. et al. Mutagenicity of fume particles from stainless steel welding. Scand J Work Environ Health 3:203-211 (1977) https://doi.org/10.5271/sjweh.2776
  7. Maxild, J. et al. Mutagenicity of fume particles from metal arc welding on stainless steel in the Salmonella /microsome test. Mutat Res 56:235-243 (1978) https://doi.org/10.1016/0027-5107(78)90190-2
  8. Antonini, J. M., Lawryk, N. J., Murthy, G. G. & Brain, J. D. Effect of welding fume solubility on lung macrophage viability and function in vitro. J Toxicol Environ Health A 58:343-363 (1999) https://doi.org/10.1080/009841099157205
  9. Taylor, M. D. et al. Effects of welding fumes of differing composition and solubility on free radical production and acute lung injury and inflammation in rats. Toxicol Sci 75:181-191 (2003) https://doi.org/10.1093/toxsci/kfg173
  10. Danielsen, T. E., Langard, S., Andersen, A. & Knudsen, O. Incidence of cancer among welders of mild steel and other shipyard workers. Br J Ind Med 50: 1097-1103 (1993)
  11. Moulin, J. J. et al. A mortality study among mild steel and stainless steel welders. Br J Ind Med 50:234-243 (1993)
  12. Barnes, P. J., Chung, K. F. & Page, C. P. Inflammatory mediators of asthma: an update. Pharmacol 50: 515-596 (1998)
  13. Massague, J. TGF-beta signal transduction. Annu Rev Biochem 67:753-791 (1998) https://doi.org/10.1146/annurev.biochem.67.1.753
  14. Bringardner, B. D., Baran, C. P., Eubank, T. D. & Marsh, C. B. The Role of inflammation in the pathogenesis of idiopathic pulmonary fibrosis. Antioxid Redox Signal 10:1-15 (2007)
  15. Kolb, M., Margetts, P. J., Sime, P. J. & Gauldie, J. Proteoglycans decorin and biglycan differentially modulate TGF-beta-mediated fibrotic responses in the lung. Am J Physiol Lung Cell Mol Physiol 280: L1327-L1334 (2001)
  16. Baran, C. P. et al. Important roles for macrophage colony-stimulating factor, CC chemokine ligand 2, and mononuclear phagocytes in the pathogenesis of pulmonary fibrosis. Am J Respir Crit Care Med 176: 78-89 (2007) https://doi.org/10.1164/rccm.200609-1279OC
  17. Cavanagh, L. L. et al. Proliferation in monocyte-derived dendritic cell cultures is caused by progenitor cells capable of myeloid differentiation. Blood 92:1598-1607 (1998)
  18. Cavanagh, L. L., Saal, R. J., Grimmett, K. L. & Thomas, R. Idiopathic pulmonary fibrosis related to endothelial injury and antiendothelial cell antibodies. Hum Immunol 67:284-297 (2006) https://doi.org/10.1016/j.humimm.2006.02.026
  19. Powell, C. L. et al. Phenotypic anchoring of acetaminophen- induced oxidative stress with gene expression profiles in rat liver. Toxicol Sci 93:213-222 (2006) https://doi.org/10.1093/toxsci/kfl030
  20. Chung, H. et al. Comprehensive analysis of differential gene expression profiles on carbon tetrachlorideinduced rat liver injury and regeneration. Toxicol Appl Pharmacol 206:27-42 (2004)
  21. Oda, H. et al. Microarray analysis of the genes induced by tetracycline-regulated expression of NDRF/ NeuroD2 in P19 cells. Biochem Biophys Res Commun 335:458-468 (2005) https://doi.org/10.1016/j.bbrc.2005.07.093
  22. Waring, J. F. et al. Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles. Toxicol Appl Pharmacol 175:28-42 (2001) https://doi.org/10.1006/taap.2001.9243
  23. Rim, K. T. et al. Gene-expression profiling of human mononuclear cells from welders using cDNA microarray. J Toxicol Environ Health A 70:1264-1277 (2007) https://doi.org/10.1080/15287390701428986
  24. Rim, K. T. et al. Gene-expression profiling using suppression-subtractive hybridization and cDNA microarray in rat mononuclear cells in response to welding-fume exposure. Toxicol Ind Health 20:77-88 (2004) https://doi.org/10.1191/0748233704th200oa
  25. Antonini, J. M., Krishna, G. G. & Brain, J. D. Responses to welding fumes: lung injury, inflammation, and the release of tumor necrosis factor-alpha and interleukin-1 beta. Exp Lung Res 23:205-227 (1997) https://doi.org/10.3109/01902149709087368
  26. Waters, M. D. & Fostel, J. M. Toxicogenomics and systems toxicology: aims and prospects. Nat Rev Genet 5:936-948 (2004) https://doi.org/10.1038/nrg1493
  27. Wetmore, B. A. & Merrick, B. A. Toxicoproteomics: proteomics applied to toxicology and pathology. Toxicol Pathol 32:619-642 (2004) https://doi.org/10.1080/01926230490518244
  28. Kalliomäki, P. L. et al. Kinetics of the metal components of intratracheally instilled stainless steel welding fume suspensions in rats. Br J Ind Med 43:112-119 (1986)
  29. Uemitsu, N. et al. Inhalation toxicity study of welding fumes: effect of single or repeated exposure on the lungs of rats. Toxicology 30:75-92 (1984) https://doi.org/10.1016/0300-483X(84)90064-7
  30. Furuie H. et al. Altered accessory cell function of alveolar macrophages: a possible mechanism for induction of Th2 secretory profile in idiopathic pulmonary fibrosis. Eur Respir J 10:787-794 (1997)
  31. Furuie, H., Yamasaki, H., Suga, M. & Ando, M. Effect of short-term stainless steel welding fume inhalation exposure on lung inflammation, injury, and defense responses in rats. Toxicol Appl Pharmacol 223:234-245 (2007) https://doi.org/10.1016/j.taap.2007.06.020
  32. Oh, J. H. et al. Gene expression profiling of early renal toxicity induced by gentamicin in mice. Mol Cell Toxicol 2:185-192 (2006)