Tarantini F, Micucci I, Bellum S, Landriscina M, Garfinkel S, Prudovsky I, Maciag T
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074.
J Biol Chem. 2001 Feb 16;276(7):5147-51. doi: 10.1074/jbc.C000714200. Epub 2000 Nov 21.
Interleukin (IL)1alpha mediates proinflammatory events through its extracellular interaction with the IL1 type I receptor. However, IL1alpha does not contain a conventional signal peptide sequence that provides access to the endoplasmic reticulum-Golgi apparatus for secretion. Thus, we have studied the release of the precursor (p) and mature (m) forms of IL1alpha from NIH 3T3 cells. We have demonstrated that mIL1alpha but not pIL1alpha was released in response to heat shock with biochemical and pharmacological properties similar to those reported for the stress-mediated release pathway utilized by fibroblast growth factor (FGF)1. However, unlike the FGF1 release pathway, the IL1alpha release pathway appears to function independently of synaptotagmin (Syt)1 because the expression of a dominant-negative form of Syt1, which represses the release of FGF1, did not inhibit the release of mIL1alpha in response to temperature stress. Interestingly, whereas the expression of both mIL1alpha and FGF1 in NIH 3T3 cells did not impair the stress-induced release of either polypeptide, the expression of both pIL1alpha and FGF1 repressed the release of FGF1 in response to temperature stress. These data suggest that the release of mIL1alpha requires proteolytic processing of its precursor form and that mIL1alpha and FGF1 may utilize similar but distinct mechanisms for export.
白细胞介素（IL）-1α通过其与I型IL-1受体的细胞外相互作用介导促炎事件。然而，IL-1α不包含可使其进入内质网-高尔基体进行分泌的传统信号肽序列。因此，我们研究了IL-1α前体（p）和成熟（m）形式从NIH 3T3细胞中的释放情况。我们已证明，mIL-1α而非pIL-1α会在热休克刺激下释放，其生化和药理学特性与成纤维细胞生长因子（FGF）-1所利用的应激介导释放途径中报道的特性相似。然而，与FGF-1释放途径不同，IL-1α释放途径似乎独立于突触结合蛋白（Syt）-1发挥作用，因为抑制FGF-1释放的显性负性形式Syt-1的表达并未抑制mIL-1α在温度应激下的释放。有趣的是，尽管NIH 3T3细胞中mIL-1α和FGF-1的表达均未损害这两种多肽在应激诱导下的释放，但pIL-1α和FGF-1的表达均抑制了FGF-1在温度应激下的释放。这些数据表明，mIL-1α的释放需要对其前体形式进行蛋白水解加工，并且mIL-1α和FGF-1可能利用相似但不同的机制进行输出。
