Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Effects of Astaxanthin on the Production of NO and the Expression of COX-2 and iNOS in LPS-Stimulated BV2 Microglial Cells

  • Choi, Seok-Keun (Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University) ;
  • Park, Young-Sam (Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University) ;
  • Choi, Dong-Kug (Department of Biotechnology, Konkuk University) ;
  • Chang, Hyo-Ihl (Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University)
  • Published : 2008.12.31
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Abstract

Astaxanthin has shown antioxidant, antitumor, and anti-inflammatory activities; however, its molecular action and mechanism in the nervous system have yet to be elucidated. We examined the in vitro effects of astaxanthin on the production of nitric oxide (NO), as well as the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Astaxanthin inhibited the expression or formation of nitric oxide (NO), iNOS and COX-2 in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Astaxanthin also suppressed the protein levels of iNOS and COX-2 in LPS-stimulated BV2 microglial cells. These results suggest that astaxanthin, probably due to its antioxidant activity, inhibits the production of inflammatory mediators by blocking iNOS and COX-2 activation or by the suppression of iNOS and COX-2 degradation.

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References

  1. Benveniste, E. N. 1997. Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J. Mol. Med. 75: 165-173 https://doi.org/10.1007/s001090050101
  2. Boujedaini, N., J. Liu, C. Thuillez, L. Cazin, and A. G. Mensah- Nyagan. 2001. In vivo regulation of vasomotoricity by nitric oxide and prostanoids during gestation. Eur. J. Pharmacol. 427: 143-149 https://doi.org/10.1016/S0014-2999(01)01233-X
  3. Boyle, E. A. and P. L. McGeer. 1990. Cellular immune response in multiple sclerosis plaques. Am. J. Pathol. 137: 575-584
  4. Chen, Y. C., S. C. Shen, W. R. Lee, W. C. Hou, L. L. Yang, and T. J. Lee. 2001. Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase- 2 gene expressions by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophages. J. Cell Biochem. 82: 537-548 https://doi.org/10.1002/jcb.1184
  5. Chun, W., H. J. Lee, P. J. Kong, G. H. Lee, I. Y. Cheong, and S. S. Kim. 2005. Synthetic wogonin derivatives suppress lipopolysaccharide-induced nitric oxide production and hydrogen peroxide-induced cytotoxicity. Arch. Pharm. Res. 28: 216-219 https://doi.org/10.1007/BF02977718
  6. Combs, C. K., J. C. Karlo, S. C. Kao, and G. E. Landreth. 2001. $\beta$-Amyloid stimulation of microglia and monocytes results in TNF-alpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J. Neurosci. 21: 1179-1188 https://doi.org/10.1523/JNEUROSCI.21-04-01179.2001
  7. Feldmann, M., F. M. Brennan, and R. Maini. 1998. Cytokines in autoimmune disorders. Int. Rev. Immunol. 17: 217-228 https://doi.org/10.3109/08830189809084493
  8. Gelman, B. B. 1993. Diffuse microgliosis associated with cerebral atrophy in the acquired immunodeficiency syndrome. Ann. Neurol. 34: 65-70 https://doi.org/10.1002/ana.410340112
  9. Gonzalez-Scarano, F. and G. Baltuch. 1999. Microglia as mediators of inflammatory and degenerative diseases. Annu. Rev. Neurosci. 22: 219-240 https://doi.org/10.1146/annurev.neuro.22.1.219
  10. Hou, R. C., H. L. Chen, J. T. Tzen, and K. C. Jeng. 2003. Effect of sesame antioxidants on LPS-induced NO production by BV2 microglial cells. Neuroreport 14: 1815-1819 https://doi.org/10.1097/00001756-200310060-00011
  11. Jeohn, G. H., C. L. Cooper, K. J. Jang, B. Liu, D. S. Lee, H. C. Kim, and J. S. Hong. 2002. Go6976 inhibits LPS-induced microglial TNFalpha release by suppressing p38 MAP kinase activation. Neuroscience 114: 689-697 https://doi.org/10.1016/S0306-4522(02)00356-1
  12. Kang, G., P. J. Kong, Y. J. Yuh, S. Y. Lim, S. V. Yim, W. Chun, and S. S. Kim. 2004. Curcumin suppresses lipopolysaccharideinduced cyclooxygenase-2 expression by inhibiting activator protein 1 and nuclear factor kappab bindings in BV2 microglial cells. J. Pharmacol Sci. 94: 325-328 https://doi.org/10.1254/jphs.94.325
  13. Kim, W. K., P. G. Jang, M. S. Woo, I. O. Han, H. Z. Piao, T. H. Joh, and H. S. Kim. 2004. A new anti-inflammatory agent KL- 1037 represses proinflammatory cytokine and inducible nitric oxide synthase (iNOS) gene expression in activated microglia. Neuropharmacology 47: 243-252 https://doi.org/10.1016/j.neuropharm.2004.03.019
  14. Kreutzberg, G. W. 1996. Microglia: A sensor for pathological events in the CNS. Trends Neurosci. 19: 312-318 https://doi.org/10.1016/0166-2236(96)10049-7
  15. McGeer, P. L., D. G. Kawamata, H. Walker, I. Akiyama, and E. G. McGeer. 1993. Microglia in degenerative neurological disease. Glia. 7: 84-92 https://doi.org/10.1002/glia.440070114
  16. Minghetti, L. and G. Levi. 1995. Induction of prostanoid biosynthesis by bacterial lipopolysaccharide and isoproterenol in rat microglial cultures. J. Neurochem. 65: 2690-2698 https://doi.org/10.1046/j.1471-4159.1995.65062690.x
  17. Phizackerley, P. J. and S. A. Al-Dabbagh. 1983. The estimation of nitrate and nitrite in saliva and urine. Anal. Biochem. 131: 242-245 https://doi.org/10.1016/0003-2697(83)90161-6
  18. Rosenbaum, J. T., H. O. McDevitt, R. B. Guss, and P. R. Egbert. 1980. Endotoxin-induced uveitis in rats as a model for human disease. Nature 286: 611-613 https://doi.org/10.1038/286611a0
  19. Schmidt, H. H. and U. Walter. 1994. NO at work. Cell 78: 919-925 https://doi.org/10.1016/0092-8674(94)90267-4
  20. Schmidt, H. W. and M. Kelm. 1996. Determination of nitrite and nitrate by the Griess reaction. In: Methods in Nitric Oxide Research, pp. 491-497. John Wiley, Sons Ltd
  21. Tha, K. K., Y. Oskuma, H. Miyazaki, T. Murayama, T. Uehara, and R. Hatakeyama. 2000. Changes in expressions of proinflammatory cytokines IL-1$\beta$TNF-$\alpha$, and IL-6 in the brain of senescence accelerated mouse (SAM) P8. Brain Res. 885: 25-31 https://doi.org/10.1016/S0006-8993(00)02883-3
  22. Tracey, K. J. and A. Cerami. 1994. Tumor necrosis factor: A pleiotropic cytokine and therapeutic target. Annu. Rev. Med. 45: 491-503 https://doi.org/10.1146/annurev.med.45.1.491
  23. Urushitani, M., S. Shimohama, T. Kihara, H. Sawada, A. Akaike, M. Ibi, et al. 1998. Mechanism of selective motor neuronal death after exposure of spinal cord to glutamate: Involvement of glutamate-induced nitric oxide in motor neuron toxicity and nonmotor neuron protection. Ann. Neurol. 44: 796-807 https://doi.org/10.1002/ana.410440514

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