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Effect of alpha-2-macroglobulin on cytokine-mediated human C-reactive protein production

Abstract

Alpha-2-macroglobulin (α2-M), a serum protease inhibitor that also binds cytokines, neutralized the inhibitory effect exerted by transforming growth factor-Β (TGF-Β) on IL-6-induced C-reactive protein (CRP) production by the human hepatoma cell line PLC/PRF/5. α2-M was found to bind noncovalently with TGF-Β to form a complex that, upon acidification, released TGF-Β inhibitory activity as detected by IL-6-induced CRP production. Although α2-M also binds IL-6, it did not alter IL-6-induced CRP production by the hepatoma cells. The interaction between α2-M and TGF-Β may influence the production of acute-phase proteins by liver hepatocytes.

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References

  1. 1.

    Gordon, A. H., andA. Koj. 1985.Acute Phase Response to Injury and Infection, Elsevier, Amsterdam.

  2. 2.

    Kushner, I. 1982. The phenomenon of the acute phase response.Ann. N. Y. Acad. Sci. 389:39.

  3. 3.

    Pepys, M. B., andM. L. Baltz. 1983. Acute phase proteins with special reference to C-reactive protein and related proteins (pentraxins) and serum amyloid A protein.Adv. Immunol. 34:141.

  4. 4.

    Balkwill, F. R., andF. Burke. 1989. The cytokine network.Immunol. Today 10:299.

  5. 5.

    Wong, G. C., andS. C. Clark. 1988. Multiple actions of IL-6 within a cytokine network.Immunol. Today 9:137.

  6. 6.

    Darlington, G. J., D. R. Wilson, andL. B. Lachman. 1986. Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hematoma cellsin vitro.J. Cell Biol. 103:787.

  7. 7.

    Goldman, N. D., andT.-Y. Liu. 1987. Biosynthesis of human C-reactive protein in cultured hepatoma cells in induced by a monocyte factor(s) other than interleukin-1.J. Biol. Chem. 262:2363.

  8. 8.

    Ganapathi, M. K., L. T. May, D. Schultz, A. Brabenec, J. Weinstein, P. B. Sehgal, andI. Kushner. 1988. Role of interleukin-6 in regulating synthesis of C-reactive protein and serum amyloid A in human hepatoma cell lines.Biochem. Biophys. Res. Commun. 150:271.

  9. 9.

    Taylor, A. W., N.-O. Ku, andR. F. Mortensen. 1989. Both human IL-1 and IL-6 induce synthesis of CRP by the PLC/PRF/5 hepatoma cell line.Ann. N. Y. Acad. Sci. 557:532.

  10. 10.

    Castell, J. V., T. Andus, D. Junz, andP. C. Heinrich. 1989. Interleukin-6: The major regulator of acute-phase protein synthesis in man and rat.Ann. N.Y. Acad. Sci. 557:87.

  11. 11.

    Moshage, H. J., H. M. J. Roelofs, J. F. Van Pelt, B. P. C. Hayenberg, M. A. Van Leeuwen, P. C. Limburg, L. A. Aarden, S. H. Yap. 1988. The effect of IL-1, IL-6 and its interrelationship on the synthesis of serum amyloid A and C-reactive protein in primary cultures of adult human hepatocytes.Biochem. Biophys. Res. Commun. 155:112.

  12. 12.

    Baumann, H. 1989. Hepatic acute phase reactionin vivo andin vitro.In Vitro Cell. Dev. Biol. 25:115.

  13. 13.

    Ganter, U., R. Arcone, C. Toniatti, G. Morrone, andG. Ciliberto. 1989. Dual control of C-reactive protein gene expression by interleukin-1 and interleukin-6.EMBO J. 8:3773.

  14. 14.

    Gewurz, H., C. Mold, J. Siegel, andB. Fiedel. 1982. C-reactive protein and the acute phase response.Adv. Intern. Med. 27:345.

  15. 15.

    Schreiber, G., A. Tsykin, A. R. Aldred, T. Thomas, W.-P. Pong, P. W. Dickson, T. Cole, H. Birch, F. A. DeJong, andJ. Milland. 1989. The acute phase response in the rodent.Ann. N.Y. Acad. Sci. 557:61.

  16. 16.

    Feldman, S. R., S. L. Gonias, andS. V. Pizzo. 1985. Model ofα2-M-macroglobulin structure and function.Proc. Natl. Acad. Sci. U.S.A. 82:5700.

  17. 17.

    Sottrup-Jensen, L. 1989.α-Macroglobulins: Structure, shape, and mechanism of proteinase complex formation.J. Biol. Chem. 264:11539.

  18. 18.

    Arakawa, H., M. Nishigai, andA. Ikai. 1989.α2-Macroglobulin traps a proteinase in the midregion of its arms.J. Biol. Chem. 264:2350.

  19. 19.

    O'Connor-McCourt, M. D., andL. M. Wakefield. 1987. Latent transforming growth factor-Β in serum: A specific complex withα 2-macroglobulin.J. Biol. Chem. 262:14090.

  20. 20.

    Matsuda, T., T. Hirano, S. Nagasawa, andT. Kishimoto. 1989. Identification ofα2-macroglobulin as a carrier protein for IL-6.J. Immunol. 142:148.

  21. 21.

    Borth, W., andT. A. Luger. 1988. Identification of aα2-macroglobulin as a cytokine binding plasma protein.J. Biol. Chem. 264:5518.

  22. 22.

    James, K. 1990. Interactions between cytokines andα2-macroglobulin.Immunol. Today 11:163.

  23. 23.

    Wahl, S. M., N. McCartney-Francis, andŚ. E. Mergenhagen. 1989. Inflammatory and immunomodulatory roles of TGF-Β.Immunol. Today 10:258.

  24. 24.

    Danielpour, D., andM. B. Sporn. 1990. Differential inhibition of transforming growth factorΒ 1 andΒ2 activity byα2-macroglobulin.J. Biol. Chem. 265:6973.

  25. 25.

    Wakefield, L. M., D. M. Smith, K. C. Flanders, andM. B. Sporn. 1988. Latent transforming growth factor-Β from human platelets.J. Biol. Chem. 263:7646.

  26. 26.

    Taylor, A. W., N.-O. Ku, andR. F. Mortensen. 1990. Regulation of cytokine-induced human C-reactive protein production by transforming growth factor-Β.J. Immunol. 145:2507.

  27. 27.

    Aden, D. P., A. Fogel, S. Plotkin, I. Domjanov, andB. B. Knowles. 1979. Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line.Nature 282:615.

  28. 28.

    May, L. T., D. C. Helfgott, andP. B. Sehgal. 1986. Anti-Β-interferon antibodies inhibit the increased expression of HLA-B7-mRNA in tumor necrosis factor treated fibroblasts of theΒ 2-interferon involved.Proc. Natl. Acad. Sci. U.S.A. 83:8957.

  29. 29.

    Wong, G. G., G. S. Witek-Giannotti, P. A. Temple, R. Kriz, C. Ferenz, R. M. Hewick, S. C. Clark, K. Ikebuchi, andM. Ogawa. 1988. Stimulation of murine hemopoietic colony formation by human IL-6.J. Immunol. 140:3040.

  30. 30.

    Derynck, R., J. A. Jarett, E. Y. Chen, D. H. Eaton, J. R. Bell, R. I. K. Assoian, A. B. Roberts, M. B. Sporn, andD. V. Goeddel. 1985. Human transforming growth factor-Β complementary DNA sequence and expression in normal and transformed cells.Nature 316:701.

  31. 31.

    Zahedi, K., J. M. Tebo, J. Siripont, G. F. Klimo, andR. F. Mortensen. 1988. Binding of human C-reactive protein to mouse macrophages is mediated by distinct receptors.J. Immunol. 142:2384.

  32. 32.

    Roberts, A. B., andM. B. Sporn. 1988. Transforming growth factor-Β.Adv. Cancer Res. 51:107.

  33. 33.

    Twardzik, D. R., J. A. Mikovits, J. E. Ranchalis, A. F. Purchio, L. Ellingsworth, andF. W. Ruscetti. 1990. γ-Interferon-induced activation of latent transforming growth factor-Β by human monocytes.Ann. N.Y. Acad. Sci. 593:276.

  34. 34.

    Debanne, M. T., R. Bell, ANDJ. Dolovich. 1976. Characteristics of the macrophage uptake of proteinase-2-macroglobulin complexes.Biochim. Biophys. Acta 428:466.

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Taylor, A.W., Mortensen, R.F. Effect of alpha-2-macroglobulin on cytokine-mediated human C-reactive protein production. Inflammation 15, 61–70 (1991). https://doi.org/10.1007/BF00917910

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Keywords

  • Public Health
  • Internal Medicine
  • Protease Inhibitor
  • Inhibitory Activity
  • Protein Production