Inhibitory Activity of Bumblebee Worker (Bombus terrestris L.) Venoms on Nitric Oxide, TNF-${\alpha}$ and IL-6 Production in Lipopolysaccharide-Activated Macrophages

  • Han Sang-Mi (Department of Agricultural Biology, National Institute of Agricultural Science and Technology, RDA) ;
  • Lee Kwang-Gill (Department of Agricultural Biology, National Institute of Agricultural Science and Technology, RDA) ;
  • Yeo Joo-Hong (Department of Agricultural Biology, National Institute of Agricultural Science and Technology, RDA) ;
  • Kweon Hae-Yong (Department of Agricultural Biology, National Institute of Agricultural Science and Technology, RDA) ;
  • Woo Soon-Ok (Department of Agricultural Biology, National Institute of Agricultural Science and Technology, RDA) ;
  • Yoon Hyung-Joo (Department of Agricultural Biology, National Institute of Agricultural Science and Technology, RDA) ;
  • Baek Ha-Ju (Gyeongsang Buk-Do Government Public Institute of Health and Environmental) ;
  • Park Kwan-Kyu (Department of Pathology, School of Medicine, Catholic University of Daegu)
  • Published : 2006.06.01

Abstract

To elucidate the composition of bumblebee (Bomb us terrestris) venom (BBV) and the anti-inflammatory effect of BBV. The major components of BBV by LC chromatography and SDS-PAGE were identified. The production of nitric oxide (NO) and proinflammatory cytokines was examined by lipopolysaccharide (LPS) in a macrophage cell line, RAW 264.7 cells, with BBV. BBV inhibits LPS-induced NO in a dose dependent manner. We also found that BBV inhibits proinflammatory cytokine, tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6 production. These findings mean that BBV can be used in controlling macrophages mediated inflammation related disease. Additional studies on the pharmacological aspects of the individual components of BBV are recommended for future trials.

Keywords

References

  1. Argiolas, A. and J. J. Pisano (1985) Bombolitins, a new class of mast cell degranulating peptides from the venom of the bumblebee Megabombus pennsylvanicus. J. Biol. Chem. 260, 1437-1444
  2. Billingham, M. E. J., J. Morley, J. M. Hanson, R. A. Shipolini and C. A. Vernon (1973) An anti-inflammatory peptide from bee venom. Nature 245, 163-164 https://doi.org/10.1038/245163a0
  3. Choi, S. H., S. K. Cho, S. S. Kang, C. S. Bae, Y. H. Bai, S. H. Lee and S. C. Pak (2003) Effect of apitherapy in piglets with preweaning diarrhea. Am. J. Chin. Med. 31, 321-326 https://doi.org/10.1142/S0192415X03001004
  4. Dotimas, E. M. and R. C. Hider (1987) Honeybee venom. Bee World 68, 51-70 https://doi.org/10.1080/0005772X.1987.11098915
  5. Faris-Eisner, R., M. P. Sherman, E. Aeberhard and G. Chaudhuri (1994) Nitric Oxide is an important mediator for tumoricidal activity in vivo. Proc. Natl. Acad Sci. 91, 9407-9411
  6. Gorman, J. D., K. E. Sack and J. C. Davis, Jr. (2002) Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N. Engl. J. Med. 346, 1349-1356 https://doi.org/10.1056/NEJMoa012664
  7. Habermann, E. (1972) Bee and wasp venoms: the biochemistry and pharmacology of their peptides and enzymes are reviewd. Science 177, 314-322 https://doi.org/10.1126/science.177.4046.314
  8. Higgs, G. A., S. Moncada and J. R. Vane (1984) Eicosanoids in inflammation. Ann. Clin. Res. 16, 287-299
  9. Hirai, Y., T. Yasuhara, T. Nakajima, M. Fujino and C. Kitada (1979) New mast cell degranulating peptide mastoparan in the venom of Vespula lewisii. Chem. Pharm. Bull. 27, 1942-1944 https://doi.org/10.1248/cpb.27.1942
  10. Hugues, M., G. Romey, D. Duval, J. P. Vincent and M. Lazdunski (1982) Apamin as a selective blocker of the calcium-dependent potassium channel in neuroblastoma cells-voltage-clamp and biochemical-channel in neuroblastoma cells-voltage-clamp and biochemical-characterization of the toxin receptor. Proc. Natl. Acad Sci. 79, 1308-1312
  11. Kim, K. S., U. S. Choi, S. D. Lee, K. H. Kim, Y. C. Chung, K. K. Park, Y. C. Lee and C. H. Kim (2005) Effects of bee venom on aromatase expression and activity in leukaemic FLG 29. 1 and primary osteoblastic cells. J. Ethnopharmacol. 99, 245-252 https://doi.org/10.1016/j.jep.2005.02.025
  12. Kondo, Y., F. Yakano and H. Hojo (1993) Inhibitory effect of bisbenzylisoquinoline alkaloids on nitrite oxide production in activated macrophages. Biochem. Pharmacol. 46, 1887-1892 https://doi.org/10.1016/0006-2952(93)90628-A
  13. Lang, F., J. M. Robert, P. Boucrot, J. Welin and J. Y. Petit (1995) New anti-inflammatory compounds that inhibit tumor necrosis factor production: Probable interaction with protein kinase C activation. J. Pharmacol. Exp. Ther. 275, 171-176
  14. Manogue, K. R., J. H. Van Denventer and A. Cerami (1992) Tumor necrosis factor-${\alpha}$ or cachectin. Academic Press
  15. Orsolic, N., L. Sver, S. Verstovsek, S. Terzic and I. Basic (2003) Inhibition of mammary carcinoma cell proliferation in vitro and tumor growth in vivo by bee venom. Toxicon 41, 861-870 https://doi.org/10.1016/S0041-0101(03)00045-X
  16. Park, E., M. R. Auinn, C. Wright and G. B. Schuller-Levis (1993) Taurine chloramines inhibits the synthesis of nitric oxide production and the release of tumor necrosis factor in activated RAW 264.7 cells. J. Leukoc Biol. 54, 119-124 https://doi.org/10.1002/jlb.54.2.119
  17. Piek, T. (1986) Venoms of the Hymenoptera. Academic Press, London
  18. Piek, T. (1991) Neurotoxic kinins from wasp and ant venoms. Toxicon. 29, 139-149 https://doi.org/10.1016/0041-0101(91)90098-C
  19. Schimmer, B. P. and K. L. Parker (2001) Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In The pharmacological basis of therapeutics. Hardman, J. G., L. E. Limbird and A. Goodman Gilman, pp. 1649-1677. McGraw-Hill, New York
  20. Stuehr, D. J., H. J. Cho, N. S. Kwon, M. Weise and C. F. Nathan (1991) Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: an FAD- and FMN-containing flavoprotein. Proc. Natl. Acad Sci. 88, 7773-7777
  21. Trikha, M., R. Corringham, B. Klein and J. F. Rossi (2003) Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: A review of the rationale and clinical evidence. Clin Cancer Res. 9, 4653-4665
  22. Vince, V., M. Brelen, J. Delbeke and I. Colin (2005) Anti-TNF-${\alpha}$ reduces the inflammatory reaction associated with cuff electrode implantation around the sciatic nerve. J. Neuroimmunol. 165, 121-128 https://doi.org/10.1016/j.jneuroim.2005.04.019