Abstract
In the previous study, galactose with C9 spacer was chemically coupled to human recombinant (rh) IL-1 alpha in order to study the effect of glycosylation on its activities, and to develop IL-1 with less deleterious effects. In this study we examined a variety of IL-1 activities in vitro, including proliferative effect on T cells, antiproliferative effect on myeloid leukemic cells and melanoma cells, stimulatory effects on IL-6 synthesis by melanoma cells and PGE2 synthesis by fibroblast cells Galactose-introduced IL-1 alpha (Gal-IL-1 alpha) exhibited reduced activities from 10 to 10000 times compared with unmodified IL-1 alpha in all the activities performed in vitro. The competitive binding of 125I-IL-1 alpha to mouse T cells and pre-B cells with unlabeled IL-1 alpha s suggests a decrease in binding affinities of Gal-IL-1 alpha to both type I and type II IL-1 receptors. Therefore, reduced activities of Gal-IL-1 alpha are due, at least partially, to the decrease in their receptor binding affinities.
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References
Dinarello CA (1996) Blood 87: 2095–147.
Fujita T, Nishikawa M, Tamaki C, Takakura Y, Hashida M, Sezaki H (1992) J Pharmacol Exp Ther 263: 971–78.
Fujita T, Furitsu H, Nishikawa M, Takakura Y, Sezaki H, Hashida M (1992) Biochem Biophys Res Commun 189: 191–96.
Takei Y, Wada K, Chiba T, Hayashi H, Ishihara H, Onozaki K (1994) ymphokine Cytokine Res 13: 265–70.
Takei Y, Wada K, Chiba T, Hayashi H, Yamada M, Kuwashima J, Onozaki K (1995) Lymphokine Cytokine Res 15: 713–19.
Takei Y, Yang D, Chiba T, Nabeshima S, Naruoka M, Wada K, Onozaki K (1996) J Interferon Cytokine Res 16: 333–36.
Drickamer K, Mamon JF, Binns G, Leuhg JO (1984) J Biol Chem 259: 770–78.
Holland EC, Leung JO, Drickamer K (1984) Proc Natl Acad Sci USA 81: 7338–42.
Spiess M, Lodish HF (1985) Proc Natl Acad Sci USA 82: 6465–6469.
Oda S, Sato M, Toyoshima S, Osawa T (1988) J Biochem (Tokyo) 104: 600–5.
Oda S, Sato M, Toyoshima S, Osawa T (1989) J Biochem (Tokyo) 105: 1040–43
Sato M, Kawakami K, Osawa T, Toyoshima S (1992) J Biochem (Tokyo) 111: 331–36.
Hopkins SJ, Humphreys M (1989) J Immunol Methods 120: 271–76.
Matsuda T, Hirano T, Kishimoto T (1988) Eur J Immunol 18: 951–56.
Mosmann T (1983) J Immunol Methods 65: 55–63
Ruff MR, Gifford GE (1980) J Immunol 125: 1671–77.
Watanabe S, Yoshida C, Kobayashi T, Okuyama H (1987) Bio Pharm Bull (in press).
Endo Y, Matsushima K, Oppenheim JJ (1986) Immunobiol 172: 316–22.
Onozaki K, Tamatani T, Hashimoto T, Matsushima K (1987) Cancer Res., 47: 2397–402.
Onozaki K, Matsushima K, Aggarwal BB, Oppenheim JJ (1995) J Immunol 135: 3962–68.
Elias JA, Lentz V (1990) J Immunol 145: 161–66.
Takii T, Akahoshi T, Kato K, Hayashi H, Marunouchi T, Onozaki K (1992) Eur J Immunol 22: 1221–27.
Sims JE, Acres RB, Grubin CE, McMahan CJ, Wignall JM, March CJ, Dower SK (1989) Proc Natl Acad Sci USA 86: 8946–50.
McMahan CJ, Slack JL, Masley B, Cosman D, Lupton SD, Brunton LL, Grubin CE, Wignall JM, Jenkins NA, Brannan Cl, Copeland NG, Huebner K, Croce CM, Cannizzarro LA, Benjamin D, Dower SK, Sproggs MK, Sims JE (1991) EMBO J 10: 2821–32.
Colotta F, Dower SK, Sims JE, Mantovani A (1994) Immunol Today 15: 562–66.
Greenfeder SA, Nunes P, Kwee L, Labow M, Chizzonite RA, Ju G (1995) J Biol Chem 270: 13757–65.
Cao Z, Henzel WJ, Gao X (1996) Sciesce 271: 1128–31.
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Nabeshima, S., Chiba, T., Takei, Y. et al. Development of glycosylated human interleukin-1 alpha, neoglyco IL-1 alpha, by coupling with D-galactose monosaccharide: biological activities in vitro. Glycoconj J 15, 69–74 (1998). https://doi.org/10.1023/A:1006943500806
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DOI: https://doi.org/10.1023/A:1006943500806