Effects of a Tetramethoxyhydroxyflavone on the Expression of Inflammatory Mediators in LPS-Treated Human Synovial Fibroblast and Macrophage Cells

  • Yoon, Do-Young (Division of Bioscience and Biotechnology, Konkuk University) ;
  • Cho, Min-Chul (Division of Bioscience and Biotechnology, Konkuk University) ;
  • Kim, Jung-Hee (Division of Bioscience and Biotechnology, Konkuk University) ;
  • Kim, Eun-Jin (Division of Bioscience and Biotechnology, Konkuk University) ;
  • Kang, Jeong-Woo (Division of Bioscience and Biotechnology, Konkuk University) ;
  • Seo, Eun-Hee (Division of Bioscience and Biotechnology, Konkuk University) ;
  • Shim, Jung-Hyun (Division of Bioscience and Biotechnology, Konkuk University) ;
  • Kim, Soo-Hyun (Institute of Biomedical Science and Technology, Konkuk University) ;
  • Lee, Hee-Gu (Korea Research Institute of Bioscience and Biotechnology) ;
  • Oh, Goo-Taeg (Division of Molecular Life Sciences, Ewha Womans University) ;
  • Hong, Jin-Tae (Department of Pharmacy, Chungbuk National University College of Pharmacy) ;
  • Park, Joo-Won (Department of Laboratory Medicine, Dankook University College of Medicine) ;
  • Kim, Jong-Wan (Department of Laboratory Medicine, Dankook University College of Medicine)
  • Published : 2008.04.30

Abstract

The inhibitory effects of 5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone (labeled as p7F) were elucidated on the productions of proinflammatory cytokines as well as inflammatory mediators in human synovial fibroblasts and macrophage cells. p7F inhibited IL-1${\beta}$ or TNF-${\alpha}$ induced expressions of inflammatory mediators (ICAM-1, COX-2, and iNOS). p7F also inhibited LPS-induced productions of nitric oxide and prostaglandin $E_2$ in RAW 264.7 cells. In order to investigate whether p7F would inhibit IL-1 signaling, p7F was added to the D10S Th2 cell line (which is responsive to only IL-1${\beta}$ and thus proliferates), revealing that p7F inhibited IL-1${\beta}$-induced proliferation of D10S Th2 cells in a dose-response manner. A flow cytometric analysis revealed that p7F reduced the intracellular level of free radical oxygen species in RAW 264.7 cells treated with hydrogen peroxide. p7F inhibited IkB degradation and NF-${\kappa}$B activation in macrophage cells treated with LPS, supporting that p7F could inhibit signaling mediated via toll-like receptor. Taken together, p7F has inhibitory effects on LPS-induced productions of inflammatory mediators on human synovial fibroblasts and macrophage cells and thus has the potential to be an anti-inflammatory agent for inhibiting inflammatory responses.

References

  1. Alcaraz, M. J. and J. R. S. Hoult. 1985. Actions of flavonoids and the novel anti-inflammatory flavone, hypolaetin-8-glucoside, on prostaglandin biosynthesis and inactivation. Biochem. Pharmacol. 34: 2477-2482 https://doi.org/10.1016/0006-2952(85)90529-5
  2. Alzoreky, N. S. and K. Nakahara. 2003. Antibacterial activity of extracts from some edible plants commonly consumed in Asia. Int. J. Food Microbiol. 15: 223-230
  3. Arend, W. P. 2001. Cytokine imbalance in the pathogenesis of rheumatoid arthritis: The role of interleukin-1 receptor antagonist. Semin. Arthritis Rheum. 30: 1-6 https://doi.org/10.1053/sarh.2001.23693
  4. Baeuerle, P. A. and V. R. Baichwal. 1997. NF-$\kappa$B as a frequent target for immunosuppressive and anti-inflammatory molecules. Adv. Immunol. 65: 111-137 https://doi.org/10.1016/S0065-2776(08)60742-7
  5. Baeuerle, P. A. and T. Henkel. 1994. Function and activation of NF-${\kappa}B$ in the immune system. Annu. Rev. Immunol. 12: 141- 179 https://doi.org/10.1146/annurev.iy.12.040194.001041
  6. Barnes, P. J. and M. Karin. 1997. Nuclear factor-${\kappa}B$- A pivotal transcription factor in chronic inflammatory diseases. N. Engl. J. Med. 336: 1066-1071 https://doi.org/10.1056/NEJM199704103361506
  7. Berenbaum, F., C. Jacques, G. Thomas, M. T. Corvol, G. Bereziat, and J. Masliah. 1996. Synergistic effect of interleukin-1 beta and tumor necrosis factor alpha on PGE2 production by articular chondrocytes does not involve PLA2 stimulation. Exp. Cell Res. 222: 379-384 https://doi.org/10.1006/excr.1996.0047
  8. Brennan, F. M. 2001. A follow-up to "Anti-cytokine therapy in chronic destructive arthritis" by Wim B. van den Berg. Arthritis Res. 3: 211-213 https://doi.org/10.1186/ar302
  9. Cho, K. J., C. H. Yun, D. Y. Yoon, Y. S. Cho, G. Rimbach, L. Packer, and A. S. Chung. 2000. Effect of bioflavonoids extracted from the bark of Pinus maritima on proinflammatory cytokine IL-1 production in LPS-stimulated Raw 264.7. Toxicol. Appl. Pharmacol. 168: 64-71 https://doi.org/10.1006/taap.2000.9001
  10. Christman, J. W., L. H. Lancaster, and T. S. Blackwell. 1998. Nuclear factor ${\kappa}B$: A pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med. 24: 1131-1138 https://doi.org/10.1007/s001340050735
  11. Cuzzocrea, S., E. Mazzon, I. Serraino, L. Dugo, T. Centorrino, A. Ciccolo, L. Sautebin, and A. P. Caputi. 2001. Celecoxib, a selective cyclo-oxygenase-2 inhibitor reduces the severity of experimental colitis induced by dinitrobenzene sulfonic acid in rats. Eur. J. Pharmacol. 431: 91-102 https://doi.org/10.1016/S0014-2999(01)01403-0
  12. Dinarello, C. A. 1997. Proinflammatory and anti-inflammatory cytokines as mediators in the pathogenesis of septic shock. Chest 112: S321-S329 https://doi.org/10.1378/chest.112.6_Supplement.321S
  13. Dinarello, C. A. 2000. Proinflammatory cytokines. Chest 118: 503-508 https://doi.org/10.1378/chest.118.2.503
  14. Egon, K., A. K. Christoph, R. Peter, C. Victor, M. Gerardo, V. Walter, and M. Irmgard. 2001. Inhibition of inflammatory cytokine production and lymphocyte proliferation by structurally different sesquiterpene lactones correlates with their effect on activation of NF-${\kappa}B$. Biochem. Pharmacol. 62: 795-801 https://doi.org/10.1016/S0006-2952(01)00714-6
  15. Geng, Y., F. J. Blanco, M. Cornelisson, and M. Lotz. 1995. Regulation of COX-2 expression in normal human articular chondrocytes. J. Immunol. 155: 796-801
  16. Guarrera, P. M. 1999. Traditional antihelmintic, antiparasitic and repellent uses of plants in Central Italy. J. Ethnopharmacol. 15: 183-192
  17. Han, Z., D. L. Boyle, A. M. Manning, and G. S. Firestein. 1998. AP-1 and NF-kappaB regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimmunity 28: 197- 208 https://doi.org/10.3109/08916939808995367
  18. Jue, D. M., K. I. Jeon, and J. Y. Jeong. 1999. Nuclear factor kappaB (NF-${\kappa}B$) pathway as a therapeutic target in rheumatoid arthritis. J. Korean Med. Sci. 14: 231-238 https://doi.org/10.3346/jkms.1999.14.3.231
  19. Karin, M. and Y. Ben-Neriah. 2000. Phosphorylation meets ubiquitination: The control of NF-${\kappa}B$ activity. Annu. Rev. Immunol. 18: 621-663 https://doi.org/10.1146/annurev.immunol.18.1.621
  20. Kim, H., S. H. Lee, K. T. Chang, T. H. Ko, K. J. Baek, and N. S. Kwon. 1995. Chloromethyl ketones block induction of nitric oxide synthase in murine macrophages by preventing activation of NF-${\kappa}B$. J. Immunol. 154: 4741-4748
  21. Kim, S., J. Cho, H. Park, C. Lim, J. Lim, H. Yun, S. Park, S. Kim, and M. Rhee. 2006. A Comparison of the antiinflammatory activity of surfactin A, B, C, and D from Bacillus subtilis. J. Microbiol. Biotechnol. 16: 1656-1659
  22. Koch, E., C. A. Klass, P. Rüngeler, V. Castro, G. Mora, and W. Vichnewski. 2001. Inhibition of inflammatory cytokine production and lymphocyte proliferation by structurally different sesquiterpene lactones correlates with their effect on activation of NF-${\kappa}B$. Biochem. Pharmacol. 62: 795-801 https://doi.org/10.1016/S0006-2952(01)00714-6
  23. Lambert, J. D. and C. S. Yang. 2003. Cancer chemopreventive activity and bioavailability of tea and tea polyphenols. Mutat. Res. 523-524: 201-208 https://doi.org/10.1016/S0027-5107(02)00336-6
  24. Lee, B. and G. Ji. 2005. Effect of Bifidobacterium cell fractions on IL-6 production in RAW 264.7 macrophage cells. J. Microbiol. Biotechnol. 15: 740-744
  25. Lee, H. G., K. A. Yu, W. K. Oh, T. W. Baeg, H. C. Oh, J. S. Ahn, W. C. Jang, J. W. Kim, J. S. Lim, Y. K. Choe, and D. Y. Yoon. 2005. Inhibitory effect of jaceosidin isolated from Artemisia argyi on the function of E6 and E7 oncoproteins of HPV. J. Ethnopharmacol. 98: 339-343 https://doi.org/10.1016/j.jep.2005.01.054
  26. Lee, H. L., M. V. Clement, and B. Halliwell. 2000. Artifacts in cell culture: Rapid generation of hydrogen peroxide on addition of (2)-epigallocatechin, (2)-epigallocatechin gallate, (1)-catechin, and quercetin to commonly used cell culture media. Biochem. Biophys. Res. Commun. 273: 50-53 https://doi.org/10.1006/bbrc.2000.2895
  27. Lennard, C. M., E. A. Mann, L. L. Sun, A. S. Chang, and W. E. Bolger. 2000. Interleukin-1 beta, interleukin-5, interleukin-6, interleukin-8, and tumor necrosis factor-alpha in chronic sinusitis: Response to systemic corticosteroids. Am. J. Rhinol. 14: 367-373 https://doi.org/10.2500/105065800779954329
  28. Lin, N., T. Sato, Y. Takayama, Y. Mimaki, Y. Sashida, M. Yano, and A. Ito. 2003. Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages. Biochem. Pharmacol. 65: 2065-2071 https://doi.org/10.1016/S0006-2952(03)00203-X
  29. Miller, C. A. 2001. Newer and safer options for osteoarthritis. Geriatr. Nurs. 22: 165-166 https://doi.org/10.1067/mgn.2001.116384
  30. Miller, M. J., W. K. MacNaughton, X. J. Zhang, J. H. Thompson, R. M. Charbonnet, P. Bobrowski, J. Lao, A. M. Trentacosti, and M. Sandoval. 2000. Treatment of gastric ulcers and diarrhea with the Amazonian herbal medicine sangre de grado. Am. J. Physiol. Gastrointest. Liver Physiol. 279: G192-G200
  31. Mills, G. B. 2002. Mechanisms underlying chemoprevention of ovarian cancer. Clin. Cancer Res. 8: 7-10
  32. O'Neill, L. A. and C. Greene. 1998. Signal transduction pathways activated by the IL-1 receptor family: Ancient signaling machinery in mammals, insects, and plants. J. Leukoc. Biol. 63: 650-657 https://doi.org/10.1002/jlb.63.6.650
  33. Pahl, H. L. 1999. Activators and target genes of Rel/NF-${\kappa}B$ transcription factors. Oncogene 18: 6853-6866 https://doi.org/10.1038/sj.onc.1203239
  34. Park, C., S. Lee, and D. Rhee. 2006. Effect of aluminum on TNF-$\alpha$ secretion from murine RAW264.7 cells for endotoxin detection in hepatitis B vaccines. J. Microbiol. Biotechnol. 16: 219-225
  35. Piela-Smith, T. H. and X. Liu. 2001. Feverfew extracts and the sesquiterpene lactone parthenolide inhibit intercellular adhesion molecule-1 expression in human synovial fibroblasts. Cell. Immunol. 209: 89-96 https://doi.org/10.1006/cimm.2001.1797
  36. Van den Berg, W. 2001. Anti-cytokine therapy in chronic destructive arthritis. Arthritis Res. 3: 18-26 https://doi.org/10.1186/ar136
  37. Yang, B., A. Kotani, K. Arai, and F. Kusu. 2001. Estimation of the antioxidant activities of flavonoids from their oxidation potentials. Anal. Sci. 17: 599-604 https://doi.org/10.2116/analsci.17.599
  38. Yang, C. S., J. M. Landau, M. T. Huang, and H. L. Newmark. 2001. Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu. Rev. Nutr. 21: 381-406 https://doi.org/10.1146/annurev.nutr.21.1.381
  39. Yang, K., S. A. Lamprecht, Y. Liu, H. Shinozaki, K. Fan, D. Leung, H. Newmark, V. E. Steele, G. J. Kelloff, and M. Lipkin. 2000. Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon. Carcinogenesis 21: 1655-1660 https://doi.org/10.1093/carcin/21.9.1655
  40. Yang, M., T. Tanaka, Y. Hirose, T. Deguchi, H. Mori, and Y. Kawada. 1997. Chemopreventive effects of diosmin and hesperidin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary-bladder carcinogenesis in male ICR mice. Int. J. Cancer 73: 719-724 https://doi.org/10.1002/(SICI)1097-0215(19971127)73:5<719::AID-IJC18>3.0.CO;2-0
  41. Yang, N., D. J. Nikolic-Paterson, Y. Y. Ng, W. Mu, C. Metz, M. Bacher, A. Meinhardt, R. Bucala, R. C. Atkins, and H. Y. Lan. 1998. Reversal of established rat crescentic glomerulonephritis by blockade of macrophage migration inhibitory factor (MIF): Potential role of MIF in regulating glucocorticoid production. Mol. Med. 4: 413-424
  42. Yoon, D. Y. and C. A. Dinarello. 1998. Antibodies to domains II and III of the IL-1 receptor accessory protein inhibit IL-1 beta activity but not binding: Regulation of IL-1 responses is via type I receptor, not the accessory protein. J. Immunol. 160: 3170-3179