Abstract
Three distinct N-terminal variants of rhIL-1β can be generated by expression of the IL-1β gene in E. coli; the naturally occurring Ala1 species, Met0-Ala1 and des-Ala1 proteins. Since most studies with rhIL-1β have used a mixture of two or more variants, we have evaluated their individual bioactivities. The variants were resolved by cation exchange HPLC. Bioactivity measurement on murine thymocytes gave a potency order of Ala1 > des-Ala1 > Met0-IL-1β. Analysis using human T-cells co-stimulated with PMA showed a potency order of Ala1 > des-Ala1 > Met0-IL-1β. Thus changes in the N-terminal amino acid of IL-1β changes the activity of the protein. Since murine and human T-cells respond similarly, the interactions between the N-terminus of rhIL-1β and their receptors probably occur through comparable mechanisms.
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Y. Kikumoto, Y.-M. Hong, T. Nishida, S. Nakai, Y. Masui and Y. Hirai,Purification and characterization of recombinant human interleukin-1β produced in Escherichia coli, Biochem. Biophys. Res. Commun.147, 321–351 (1987).
D. B. Carter, K. A. Curry, C.-S. C. Tomich, A. W. Yem, M. R. Deibel, D. E. Tracey, J. W. Paslay, J. B. Carter, N. Y. Theriault, P. K. Harris, I. M. Reardon, H. A. Zurcher-Neely, R. L. Heinrickson, L. L. Clancy, S. W. Muchmore, K. D. Watenpaugh and H. M. Einspahr,Proteins: Structure, Function and Genetics,3, 121–129 (1988).
S. R. Kronheim, M. A. Cantrell, M. C. Deeley, C. J. March, P. J. Glackin, D. M. Anderson, T. Hemenway, J. E. Merriam, D. Cosman and T. P. Hop,Purification and characterization of human interleukin-1 expressed in Escherichia coli, Biotechnology4, 1078–1082 (1986).
P. Wingfield, M. Payton, J. Tavernier, M. Barnes, A. Shaw, K. Rose, G. Simona, S. Demczuk, K. Williamson and J.-M. Dayer,Purification and characterization of human interleukin-1β expresed in recombinant Escherichia coli, Eur. J. Biochem.160, 491–497 (1986).
P. Wingfield, P. Graber, N. RaoMovva, A. M. Gronenborn and H. Robson MacDonald,N-terminal-methionylated interleukin-1β has reduced receptor-binding affinity. FEBS letters215, 160–164 (1987).
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Richard, K.A., Yem, A.W., Deibel, M.R. et al. Isolation and bioactivities of three IL-1β N-terminal variants. Agents and Actions 27, 268–270 (1989). https://doi.org/10.1007/BF01972793
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DOI: https://doi.org/10.1007/BF01972793