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The Discovery and Characterization of an Interleukin 6 Cytokine Family Antagonist Protein from A Marine Sponge, Callyspongia sp.

  • Jane V. Peppard
  • Patricia Loo
  • Matthew A. Sills
  • Lawrence Wennogle
  • Amy Wright
  • Shirley Pomponi
  • Maria Cueto
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 484)

Abstract

The process of drug discovery in the pharmaceutical industry often begins with the setting up of a bioassay whereby many thousands of synthetic compounds, or less characterized substances such as natural product extracts, may be screened in high throughput mode. During the early 1990s, we started a search using this approach for inhibitors of the cytokine Interleukin 6 (IL-6). One of the sources for screening was extracts of marine organisms provided to the former Ciba-Geigy organization by Harbor Branch Oceanographic Institute (HBOI). This chapter describes the finding of activity inhibiting IL-6 function from an extract of the marine sponge Callyspongia sp., and work which was carried out during the effort to characterize this activity more fully.

Keywords

HepG2 Cell Marine Sponge Sponge Extract Natural Product Extract Immunoglobulin Secreting Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Hirano, T. and Kishimoto, T. 1992. Molecular biology and immunology of interleukin-6 (46th Forum in Immunology). Res. Immunol. 143:723PubMedCrossRefGoogle Scholar
  2. 2.
    Hirano, T. 1992. Interleukin-6 and its relation to inflammation and disease. Clin. Immunol & Immunopathol. 62:860.Google Scholar
  3. 3.
    Breen, E.C., Rezai, A. R., Nakajima, K., Beall, G.N., Mitsuyasu, R.T., Hirano, T., Kishimoto, T. and Martinez-Maza, 0. 1990. Infection with HIV is associated with elevated IL-6 levels and production. J. Immunol. 144:480.PubMedGoogle Scholar
  4. 4.
    Jilka, R.L., Hangoc, G., Girasole, G., Passeri, G., Williams, D.C., Abrams, J., Boyce, B., Broxmeyer, H. and Manolagas, S. 1992. Increased osteoclast development after estrogen loss: mediation by Interleukin-6. Science 257:88.PubMedCrossRefGoogle Scholar
  5. 5.
    Taga, T., Hibi, M., Hirata, Y., Yamasaki, K., Yasukawa, K., Matsuda, T., Hirano, T. and Kishimoto, T. 1989. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 58:573.PubMedCrossRefGoogle Scholar
  6. 6.
    Simpson, R.J., Hammacher, A., Smith, D.K., Matthews, J.M. and Ward, L.D. 1997. Interleukin-6: structure-function relationships. Protein Sci. 6:929PubMedCrossRefGoogle Scholar
  7. 7.
    Murakami, M., Hibi, M., Nakagawa, N., Nagakawa, T., Yasukawa, K., Yamanishi, K, Taga, T. and Kishimoto, T. 1993. IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science 260:1808.PubMedCrossRefGoogle Scholar
  8. 8.
    Hirano, T., Nakajima, K. and Hibi, M. 1997. Signaling mechanisms through gp 130: a model of the cytokine system. Cytokine & Growth Factor Rev. 8:241.CrossRefGoogle Scholar
  9. 9.
    Heinrich, P.C., Bchrmann, I., Muller-Newen, G., Scahper, F. and Graeve, L. 1998. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem. J. 334:297.PubMedGoogle Scholar
  10. 10.
    Taga, T., Kawanishi, K., Hardy, R.R., Hirano, T. and Kishimoto, T. 1987. Receptors for B cell stimulatory factor 2. Quantitation, specificity, distribution, and regulation of their expression. J. Exp. Med. 166:967.PubMedCrossRefGoogle Scholar
  11. 11.
    Peppard, J.V., Loo, P., Sills, M.A.., Munster, D., Pompon, S.A. and Wright, A. E. 1996. Characterization of an interleukin 6 cytokine family antagonist protein from a marine sponge, Callyspongia sp. J Biol. Chem. 271:7281.PubMedCrossRefGoogle Scholar
  12. 12.
    Pomponi, S.A. 1976. A cytological study of the Haliclonidae and the Calyspongiidae (Porifera, Desmospongiae, Haplosclerida). In: “Aspects of Sponge Biology”, Eds. F.W. Harrison and R.R. Cowden, Academic Press.Google Scholar
  13. 13.
    Peppard, J.V., Smith, H.D. and Zhou, S. 1994. Kinetics of a cellular response to Interleukin 6. Cell. Immunol. 155:253.PubMedCrossRefGoogle Scholar
  14. 14.
    Yoshida, K., Taga, T., Saito, M., Suematsu, S., Kumanogoh, A., Tanaka, T., Fujiwara, H., Hirata, M., Yamagami. T„ Nakahata, T., Hirabayashi, T., Yoneda, Y., Tanaka, K., Wang, W.Z, Mori, C., Shiota, K., Yoshida, N. and Kishimoto, T. 1996. Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders. Proc. Natl. Acad. Sci. U.S.A. 93:407.PubMedCrossRefGoogle Scholar
  15. 15.
    Betz, U.A.K., Bloch, W., van den Broeck, M., Yoshida, K., Taga, T. Kishimoto, T., Addicks, K., Rajewsky, K. and Muller, W. 1998. Postnatally induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic, immunolgocial, hepatic and pulmonary defects. J. Exp. Med. 188: 1955.Google Scholar
  16. 16.
    Yamamori, T. and Sarai, A. 1992. Coevolution of cytokine receptor families in the immune and nervous system. Neurosci. Res. 15: 151.Google Scholar
  17. 17.
    Kallen, K-J., Grotzingcr, J., Lelievre E., Vollmer, P., Aasland, D., Renne, C., Mullberg, J., Meyer zum Buschenfelde, K-H., Gasean, H. and Rose-John, S. 1999. Receptor recognition sites of cytokines are organized as exchangeable modules. J. Biol. Chem. 274:11859.PubMedCrossRefGoogle Scholar
  18. 18.
    Huang, Y.W. and Vitetta, E.S. 1995 Immunotherapy of multiple myeloma. Stem Cells 13:123.PubMedCrossRefGoogle Scholar
  19. 19.
    Brackenhoff, J.P.J., de Hon. F.D., Fontaine, V., ten Boekel, E., Schooltink, H., Rose-John, S., Heinrich, P.C., Content, J. and Aarden, L.A. 1994. Development of a human interleukin-6 receptor antagonist. J Biol. Chem. 269: 86.Google Scholar
  20. 20.
    Sporcno, E., Savino, R., Ciapponi, L., Paonessa, G., Cabibo, A., Lahm, A., Pulkki, K., Sun, R-X., Toniatti, C., Klein, B. and Cilikberto, G. 1996. Human Interleukin-6 receptor super-antagonists with high potency and wide spectrum on multiple myeloma cells. Blood 87:4510.Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Jane V. Peppard
    • 1
  • Patricia Loo
    • 1
  • Matthew A. Sills
    • 1
  • Lawrence Wennogle
    • 1
  • Amy Wright
    • 1
    • 2
  • Shirley Pomponi
    • 1
    • 2
  • Maria Cueto
    • 1
  1. 1.Novartis Institute for Biomedical ResearchUSA
  2. 2.Harbor Branch Oceanographic InstituteUSA

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