Abstract
We have previously shown that changes in acute-phase protein glycosylation result from alterations occurring within hepatocytes as a result of regulation by cytokines, that the glycosylation patterns of proteins secreted by Hep 3B and Hep G2 cells respond differently to the crude mixtures of cytokines found in conditioned medium from LPS-stimulated monocytes, and that interleukin-6 (IL-6) causes increased concanavalin A (Con A) binding ofαl protease inhibitor in Hep 3B cells and decreased Con A binding of this protein in Hep G2 cells. In the present study we found that transforming growth factorΒl (TGF-Β), like IL-6, led to secretion of forms ofαl-protease inhibitor with increased Con A binding in Hep 3B cells, and that IL-6 and TGF-Β in combination were additive. In contrast, in Hep G2 cells, TGF-Β had an effect opposite to that produced by IL-6, leading to secretion of forms ofαl-protease inhibitor with increased Con A binding. When employed in combination with IL-6, TGF-Β abolished the effect of that cytokine. These studies indicate that TGF-Β influences glycosylation of al-protease inhibitor in two human hepatoma cell lines in a manner that can be differentiated from that of IL-6. The identification of TGF-Β as a second defined cytokine capable of influencing glycoprotein glycosylation and the demonstration that the effect of one cytokine can be modulated by another cytokine support the view that changes in glycosylation of plasma proteins are mediated by combinations of cytokines.
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References
Kushner, I. 1982. The phenomenon of the acute phase response.Ann. N. Y. Acad. Sci. 389:39.
Kushner, I., andA. Mackiewicz. 1987. Acute phase proteins as disease markers.Dis. Markers 5:1.
Baumann, H. 1989. Hepatic acute phase reaction in vivo and in vitro.In Vitro Cell. Dev. Biol. 25:115.
Baenziger, J. U. 1984.In The Plasma Proteins. F. Putnam, editor. Academic Press, New York. 271–316.
Hatton, M. W., L. Marz, andE. Regoeczi. 1983. On the significance of heterogeneity of plasma glycoproteins possessingN-glycans of the complex type-a perspective.Trends Biochem. Sci. 8:287.
Nicollet, I., J. P.Leberton, M.Fontane, and M.Hirou. Evidence for alpha-1-acide glycoprotein populations of different pI values after concanavalin A affinity chromatography. Study of their evolution during inflammation in man. 1981.Biochim. Biophys. Acta 668:235.
Raynes, J. 1982. Variations in the relative proportions of microheterogeneous forms of plasma glycoproteins in pregnanacy and disease.Biomedicine (Paris) 36:77.
Mackiewicz, A., T. Pawlowski, A. Mackiewicz-Pawlowska, K. Wiktorowicz, andS. Mackiewicz. 1987. Microheterogeneous forms of alpha-1-acid glycoprotein as indicators of rheumatoid arthritis activity. 1987.Clin. Chim. Acta 163:185.
Mackiewicz, A., R. Marcinkowska-Pieta, S. Ballou, S. Mackiewicz, andI. Kushner. 1987. Microheterogeneity of alpha-1-acid glycoprotein in detection of intercurrent infection in systemic lupus erythematosus.Arthritis Rheum. 30:513.
Pawlowski, T., S. Mackiewicz, andA. Mackiewicz. 1989. Microheterogeneity of alpha1-acid glycoprotein in the detection of intercurrent infection in patients with rheumatoid arthritis.Arthritis Rheum. 32:347.
Hansen, J. E. S., S. P. Jensen, B. Nörgaard-Pedersen, andT. C. Bög-Hansen. 1986. Electrophoretic analysis of the glycan microheterogeneity of orosomucoid in cancer and inflammation.Electrophoresis 7:180.
Hachulla, E., A. Laine, andA. Hayem. 1988.α 1-Antichymotrypsin microheterogeneity in crossed immunoaffinoelectrophoresis with free concanavalin A: A useful tool in inflammatory syndrome.Clin. Chem. 34/5:911.
Vaughan, L., M. A. Loner, andR. W. Carrell. 1982.α 1-Antitrypsin microheterogeneity. Isolation and physiological significance of isoforms.Biochim. Biophys. Acta 701:339.
Bierhuizen, M. F. A., M. De Wit, C. A. R. L. Govers, W. Ferwerda, C. Koelman, O. Pos, andW. Van Dijk. 1988. Glycosylation of three molecular forms of humanα 1acid glycoprotein having different interactions with concanavalin A. Variations in the occurrence of di-, tri-, and tetraantennary glycans and the degree of sialylation.Eur. J. Biochem. 175:387.
Mackiewicz, A., M. A. Khan, T. L. Reynolds, S. Van Der Linden, andI. Kushner. 1989. Serum IgA, acute phase proteins, and glycosylation ofα 1-acid glycoprotein in ankylosing spondylitis.Ann. Rheum. Dis. 48:99.
Jezequel, M., N. S. Seta, M. M. Corbic, J. M. Feger, andG. M. Durand. 1988. Modification of concanavalin A patterns of alpha-1-acid glycoprotein and alpha 2-HS glycoprotein in alchoholic liver disease.Clin. Chim. Acta 176:49.
Mackiewicz, A., M. K. Ganapathi, D. Schultz, andI. Kushner. 1987. Monokines regulate glycosylation of acute-phase proteins.J. Exp. Med. 166:253.
Mackiewicz, A., D. Schultz, J. Mathison, M. Ganapathi, andI. Kushner. 1989. Effect of cytokines on glycosylation of acute phase proteins in human hepatoma cell lines.Clin. Exp. Immunol. 75:70.
Mackiewicz, A., andI. Kushner. 1989. InterferonΒ 2/B-cell stimulating factor 2/interleukin 6 affects glycosylation of acute phase proteins in human hepatoma cell lines.Scand. J. Immunol. 29:265.
Mackiewicz, A., andI. Kushner. 1989. Role of IL-6 in acute phase protein glycosylation.Ann. N.Y. Acad. Sci. 557:515.
Pos, O., H. J. Moshage, S. H. Yap, J. P. M. Schnieders, L. A. Aarden, J. Van Gool, W. Boers, A. M. Brugman, andW.Van Dijk. 1989. Effects of monocytic products, recombinant interleukin-1, and recombinant interleukin-6 on glycosylation ofα 1-acid glycoprotein.Inflammation 13:415.
Mackiewicz, A., M. K. Ganapathi, D. Schultz, A. Brabenec, J. Weinstein, M. F. Kelley, andI. Kushner. 1990. Transforming growth factorΒ regulates production of acute phase proteins.Proc. Natl. Acad. Sci. U.S.A. 87:1491.
Laurel, C. B., Electroimmunoassay. 1972.Scand. J. Clin. Lab. Invest. Suppl. 124:21.
Ganapathi, M. K., D. Schultz, A. Mackiewicz, D. Samols, S.-I. Hu, A. Brabenec, S. Macintyre, andI. Kushner. 1988. Heterogenous nature of the acute phase response.J. Immunol. 141:564.
Mackiewicz, A., andS. Mackiewicz. 1986. Determination of lectin sugar dissociation constants by agarose affinity electrophoresis.Anal. Biochem. 156:481.
Bog-Hansen, T. C., andK. Takeo. 1980. Determination of dissociation constants by affinity electrophoresis: Complexes between human serum proteins and concanavalin A.Electrophoresis 1:67.
Assoian, R. K., A. Komoriya, C. A. Meyers, D. M. Miller, andM. B. Sporn. 1980. Transforming growth factor-Β in human platelets.J. Biol. Chem. 258:7155.
Assioan, R. K., B. E. Fleurdelys, H. C. Stevenson, P. J. Miller, D. K. Madtes, E. W. Raines, R. Ross, andM. B. Sporn. 1987. Expression and secretion of type beta transforming growth factor by activated human macrophages.Proc. Natl. Acad. Sci. U.S.A. 84:6020.
Kehrl, J. H., L. M. Wakefield, A. B. Roberts, S. Jakowlew, M. Alvarez-Mon, R. Derynck, M. B. Sporn, andA. S. Fauci. 1986. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.J. Exp. Med. 163:1037.
Roberts, A. B., andM. B. Sporn. 1988. Transforming growth factorΒ 1.Adv. Cancer Res. 51:107.
Edwards, D. R., G. Murphy, J. J. Reynolds, S. E. Whitham, A. J. Docherty, P. Angel, andJ. K. Heath. 1987. Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor.EMBO J. 6:1899.
Laiho, M., O. Saksela, andJ. Keski-Oja. 1987. Transforming growth factor-Β induction of type-1 plasminogen activator inhibitor.J. Biol. Chem. 263:17467.
Mega, T., E. Lujan, andA. Yoshida. 1980. Studies on the oligosaccharide chains of humanα 1-proteinase inhibitor.J. Biol. Chem. 225:4057.
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Mackiewicz, A., Kushner, I. Transforming growth factor Β1 influences glycosylation of α1-protease inhibitor in human hepatoma cell lines. Inflammation 14, 485–497 (1990). https://doi.org/10.1007/BF00914270
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DOI: https://doi.org/10.1007/BF00914270