三种白细胞介素-1β N端变体的分离及其生物活性

Isolation and bioactivities of three IL-1 beta N-terminal variants.

作者信息

Richard K A, Yem A W, Deibel M R, Staite N D

机构信息

Department of Hypersensitivity Diseases, Upjohn Company, Kalamazoo, MI 49001.

出版信息

Agents Actions. 1989 Jun;27(3-4):268-70. doi: 10.1007/BF01972793.

DOI:10.1007/BF01972793

PMID:2801309

Abstract

Three distinct N-terminal variants of rhIL-1 beta can be generated by expression of the IL-1 beta gene in E. coli; the naturally occurring Ala1 species, Met0-Ala1 and des-Ala1 proteins. Since most studies with rhIL-1 beta 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 greater than des-Ala1 greater than Met0-IL-1 beta. Analysis using human T-cells co-stimulated with PMA showed a potency order of Ala1 greater than des-Ala1 greater than Met0-IL-1 beta. Thus changes in the N-terminal amino acid of IL-1 beta changes the activity of the protein. Since murine and human T-cells respond similarly, the interactions between the N-terminus of rhIL-1 beta and their receptors probably occur through comparable mechanisms.

摘要

通过在大肠杆菌中表达白细胞介素-1β（IL-1β）基因，可以产生三种不同的N端变体；天然存在的Ala1型、Met0-Ala1和去Ala1蛋白。由于大多数关于重组人白细胞介素-1β（rhIL-1β）的研究使用了两种或更多变体的混合物，我们评估了它们各自的生物活性。这些变体通过阳离子交换高效液相色谱法进行分离。对小鼠胸腺细胞的生物活性测量得出的效力顺序为Ala1大于去Ala1大于Met0-IL-1β。使用佛波酯（PMA）共刺激的人T细胞进行分析显示的效力顺序为Ala1大于去Ala1大于Met0-IL-1β。因此，IL-1β的N端氨基酸变化会改变该蛋白的活性。由于小鼠和人T细胞的反应相似，rhIL-1β的N端与其受体之间的相互作用可能通过类似的机制发生。