Toxicological Research

  • 제20권3호
  • /
  • Pages.233-239
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  • 2004
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  • 1976-8257(pISSN)
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  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
권호 표지

Differential Alterations of Endotoxin-induced Cytokine Expression and Mitogen-activated Protein Kinase Activation by Mercury in Mouse Kidney

  • Kim, Sang-Hyun (Research Center for Resistant Cells, College of Medicine, Chosun University, Interdisciplinary Program of Toxicology, Department of Physiology and Pharmacology, The University of Georgia) ;
  • Kim, Dae-Keun (College of Pharmacy, Woosuk University) ;
  • Shin, Tae-Yong (College of Pharmacy, Woosuk University) ;
  • Choi, Cheol-Hee (Research Center for Resistant Cells, College of Medicine, Chosun University)
  • 발행 : 2004.09.01
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초록

The present study was designed to determine the impact of mercury on endotoxin-induced inflammatory cytokine expression and corresponding signal transduction in mouse kidney. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercury in drink-ing water for 14 days and at the end of the treatment period, lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 h prior to euthanasia. The doses of mercury and LPS did not cause hepatotoxicity or renal toxicity as indicated by unaltered plasma alanine aminotransferase and aspartate aminotransferase levels, and terminal UTP nucleotide end-labeling assay from kidney, respectively. Mercury decreased kidney glutathione (GSH) and with LPS, it additively decreased GSH. Mercury activated p38 mitogen-activated protein kinase (MAPK) and additively increased LPS-induced p38 MAPK phosphorylation. In contrast, mercury inhibited LPS-induced activation of extra-cellular signal-regulated kinase (ERK) but had no effect alone. Mercury increased the gene expression of tumor necrosis factor $\alpha$ (TN F$\alpha$) and potentiated LPS-induced TNF$\alpha$ expression. Mercury did not affect LPS-induced interleukin-1$\beta$ (IL-1$\beta$) expression but decreased LPS-induced IL-6 expression. These results suggest that low levels of mercury might augment LPS-induced TNF$\alpha$ expression by altering GSH and p38 MAPK. Mercury modulates LPS-induced p38 and ERK activation, and downstream TNF$\alpha$ and IL-6 expression in kidney, respectively.

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참고문헌

  1. Arbabi, S. and Maier, R.V. (2002): Mitogen-activated protein kinases. Crit. Care. Med., 30, S74-S79
  2. Baker, M.A., Cerniglia, G.J. and Zaman, A (1990): Microtiter plate assay for the measurement of glutathione and glutathione disulfide in large numbers of biological samples. Anal. Biochem., 190, 360-365
  3. Chen, C.C. and Wang, J.K. (1999): p38 but not p44/42 mitogen-activated protein kinase is required for nitric oxide synthase induction mediated by lipopolysaccharide in RAW 264.7 macrophages. Mol. Pharmacol., 55, 481-488
  4. Dong, C., Davis, R.J. and Flavell, R.A. (2002): MAP kinases in the immune response. Annu. Rev. Immunol., 20, 55-72
  5. Farina, M., Brandao, R., de Lara, F.S., Pagliosa, L.B., Soares, F.A, Souza, D.O. and Rocha, J.B. (2003): Profile of nonprotein thiols, lipid peroxidation and delta-aminolevulinate dehydratase activity in mouse kidney and liver in response to acute exposure to mercuric chloride and sodium selenite. Toxicology, 184, 179-187
  6. Feng, G.J., Goodridge, H.S., Harnett, M.M., Wei, X.Q., Nikolaev, A.V., Higson, A.P. and Liew, F.Y. (1999): Extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases differentially regulate the lipopolysaccharide-mediated induction of inducible nitric oxide synthase and IL-12 in macrophages: Leishmania phosphoglycans subvert macrophage IL-12 production by targeting ERK MAP kinase. J. Immunol., 163, 6403-6412
  7. Ghosh, S., Latimer, R.D., Gray, B.M., Harwood, R.J. and Oduro, A. (1993): Endotoxin-induced organ injury. Crit. Care. Med., 21, S19-24
  8. Gilot, D., Loyer, P., Corlu, A., Glaise, D., Lagadic-Gossmann, D., Atfi, A., Morel, F., Ichijo, H. and Guguen-Guillouzo, C. (2002): Liver protection from apoptosis requires both blockage of initiator caspase activities and inhibition of ASK1/JNK pathway via glutathione S-transferase regulation. J. Biol. Chem., 277, 49220-49229 https://doi.org/10.1074/jbc.M207325200
  9. Goering, P.L., Morgan, D.L. and Ali, S.F. (2002): Effects of mercury vapor inhalation on reactive oxygen species and antioxidant enzymes in rat brain and kidney are minimal. J. Appl. Toxicol., 22, 167-172 https://doi.org/10.1002/jat.844
  10. Gordon, S. (1998): The role of the macrophage in immune regulation. Res. Immunol., 149, 685-688
  11. Haddad, J.J. (2002): The involvement of L-gamma-glutamylL- cysteinyl-glycine (glutathione/GSH) in the mechanism of redox signaling mediating MAPK(p38)-dependent regulation of pro-inflammatory cytokine production. Biochem. Pharmacol., 63, 305-320
  12. Hewett, J.A. and Roth, R.A. (1993): Hepatic and extrahepatic pathobiology of bacterial Iipopolysaccharides. Pharmacol. Rev., 45, 382-411
  13. Hussain, S., Atkinson, A., Thompson, S.J. and Khan, A.T.(1999): Accumulation of mercury and its effect on antioxidant enzymes in brain, liver, and kidneys of mice. J. Environ. Sci. Health B, 34, 645-660 https://doi.org/10.1080/03601239909373219
  14. Johnson, V.J. and Sharma, R.P. (2001): Gender-dependent immunosuppression following subacute exposure to fumonisin B1. Int. Immunopharmacol., 1, 2023-2034
  15. Kim, S.H., Johnson, V.J. and Sharma, R.P. (2002). Mercury inhibits nitric oxide production but activates proinflammatory cytokine expression in murine macrophage: differential modulation of NF-kappaB and p38 MAPK signaling pathways. Nitric. Oxide., 7, 67-74 https://doi.org/10.1016/S1089-8603(02)00008-3
  16. Kim, S.H., Kim, J. and Sharma, R.P. (2004). Inhibition of p38 and ERK MAP kinases blocks endotoxin-induced nitric oxide production and differentially modulates cytokine expression. Pharmacol. Res., 49, 433-439 https://doi.org/10.1016/j.phrs.2003.11.004
  17. Koropatnick, J. and Zalups, R.K. (1997): Effect of non-toxic mercury, zinc or cadmium pretreatment on the capacity of human monocytes to undergo lipopolysaccharide-induced activation. Br. J. Pharmacol., 120, 797-806 https://doi.org/10.1038/sj.bjp.0700975
  18. Lee, J.C., Laydon, J.T., McDonnell, P.C., Gallagher, T.F., Kumar, S., Green, D., McNulty, D., Blumenthal, M.J., Heys, J.R., Landvatter, S.W. and et al. (1994): A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature, 372, 739-746 https://doi.org/10.1038/372739a0
  19. Lee, J.C. and Young, P.R. (1996): Role of CSB/p38/RK stress response kinase in LPS and cytokine signaling mechanisms. J. Leukoc. Biol., 59, 152-157
  20. Nguyen, V.A. and Gao, B. (1999): Cross-talk between alpha(1B)-adrenergic receptor (alpha(1B)AR) and interleukin- 6 (IL-6) signaling pathways. Activation of alpha(1b)AR inhibits il-6-activated STAT3 in hepatic cells by a p42/44 mitogen-activated protein kinase-dependent mechanism. J. Biol. Chem., 274, 35492-35498 https://doi.org/10.1074/jbc.274.50.35492
  21. Shenker, B.J., Mayro, J.S., Rooney, C., Vitale, L. and Shapiro, I.M. (1993): Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. IV. Alterations in cellular glutathione content. Immunopharmacol. Immunotoxicol., 15, 273-290
  22. Tchounwou, P.B., Ayensu, W.K., Ninashvili, N. and Sutton, D. (2003): Environmental exposure to mercury and its toxicopathologic implications for public health. Environ. Toxicol., 18, 149-175
  23. Ueda, S., Masutani, H., Nakamura, H., Tanaka, T., Ueno, M. and Yodoi, J. (2002): Redox control of cell death. Antioxid. Redox. Signal., 4, 405-414
  24. Watters, J.J., Sommer, J.A., Pfeiffer, Z.A., Prabhu, U., Guerra, A.N. and Bertics, P.J. (2002): A differential role for the mitogen-activated protein kinases in lipopolysaccharide signaling: the MEK/ERK pathway is not essential for nitric oxide and interleukin 1beta production. J. Biol. Chem., 277, 9077-9087
  25. Zalups, R.K. (2000): Molecular interactions with mercury in the kidney. Pharmacol. Rev., 52, 113-143
  26. Zalups, R.K., Barfuss, D.W. and Lash, L.H. (1999): Disposition of inorganic mercury following biliary obstruction and chemically induced glutathione depletion: dispositional changes one hour after the intravenous administration of mercuric chloride. Toxicol. Appl. Pharmacol., 154, 135-144