A NOVEL SECRETORY PATHWAY FOR INTERLEUKIN-1-BETA, A PROTEIN LACKING A SIGNAL SEQUENCE
A NOVEL SECRETORY PATHWAY FOR INTERLEUKIN-1-BETA, A PROTEIN LACKING A SIGNAL SEQUENCE
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DOI：
10.1002/j.1460-2075.1990.tb08268.x
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发表时间：
1990-05-01
期刊：
影响因子：
11.4
通讯作者：
SITIA, R
中科院分区：
文献类型：
--
作者：
RUBARTELLI, A;COZZOLINO, F;SITIA, R
白细胞介素1（IL-1）是炎症的主要可溶性介质。两个人IL-1基因α和β，已经分离出，其编码仅具有20-30%氨基酸序列同源性的多肽。与大多数分泌的蛋白质不同，这两种细胞因子没有信号序列，鉴于它们的生物学作用，这是一个意想不到的发现。在这里，我们表明IL-1 β.由活化的人单核细胞通过不同于经典内质网sbd.高尔基体途径的分泌途径主动分泌。阻断IL-6、肿瘤坏死因子α的细胞内转运的药物。和其它分泌蛋白质的表达不抑制IL-1 β的分泌。IL-1 β的分泌被甲胺、低温或无血清培养基阻断，并通过将培养温度升高至42 ℃或通过钙离子载体、布雷菲德菌素A、莫能菌素、二硝基苯酚或羰基氰氯苯腙的存在而增加。IL-1.beta.部分包含在胞内囊泡内，保护其免受蛋白酶消化。在U937细胞中，有，但没有秘密。在这些细胞中，IL-1 β。在囊泡部分中没有发现，并且所有的蛋白质都可以被蛋白酶消化。这表明含有IL-β的细胞内囊泡在细胞内是不稳定的。是蛋白质分泌途径的一部分。我们得出结论，IL-1 β.由活化的单核细胞通过一种新的分泌机制释放，该机制可能涉及细胞内膜的移位，并在应激条件下增加。
Interleukin 1 (IL-1) is a major soluble mediator of inflammation. Two human IL-1 genes .alpha. and .beta., have been isolated, which encode polypeptides with only 20-30% amino acid sequence homology. Unlike most secreted proteins, the two cytokines do not have a signal sequence, an unexpected finding in view of their biological role. Here we show that IL-1.beta. is actively secreted by activated human monocytes via a pathway of secretion different from the classical endoplasmic reticulum.sbd.Golgi route. Drugs which block the intracellular transport of IL-6, of tumour necrosis factor .alpha. and of other secretory proteins do not inhibit secretion of IL-1.beta.. Secretion of IL-1.beta. is blocked by methylamine, low temperature or serum free medium, and is increased by raising the culture temperature to 42.degree.C or by the presence of calcium ionophores, brefeldin A, monensin, dinitrophenol or carbonyl cyanide chlorophenylhydrazone. IL-1.beta. is contained in part within intracellular vesicles which protect it from protease digestion. In U937 cells large amounts of IL-1.beta. are made but none is secreted. In these cells IL-1.beta. is not found in the vesicular fraction, and all the protein is accessible to protease digestion. This suggests that intracellular vesicles that contain IL-.beta. are part of the protein secretory pathway. We conclude that IL-1.beta. is released by activated monocytes via a novel mechanism of secretion which may involve translocation of intracellular membranes and is increased by stress conditions.