Caspase 3 inactivates biologically active full length interleukin-33 as a classical cytokine but does not prohibit nuclear translocation
Caspase 3 inactivates biologically active full length interleukin-33 as a classical cytokine but does not prohibit nuclear translocation
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DOI：
10.1016/j.bbrc.2009.12.107
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发表时间：
2010-01-15
影响因子：
3.1
通讯作者：
Martin, Michael Uwe
中科院分区：
文献类型：
--
作者：
Ali, Shafaqat;Nguyen, Dang Quan;Martin, Michael Uwe
IL-33是IL-1细胞因子家族中的一员，具有双重功能，既可以通过IL-33受体旁分泌激活细胞，也可以移位到细胞核内调节基因转录。我们发现全长的小鼠IL-33作为一种细胞因子是活性的，并且它不被caspase I处理成成熟的IL-33，而是被caspase 3在aa175处切割产生两个都不能与IL-33受体结合的产物。然而，全长的IL-33及其N端的caspase3裂解产物转位到细胞核。最后，生物活性的IL-33不会被细胞结构性地或在激活后释放。这表明IL-33不是一种经典的细胞因子，而是在完整细胞的核中发挥作用，在产生的细胞被破坏后，仅通过其受体作为警报介质激活其他细胞。(C)2009 Elsevier Inc.保留所有权利。
IL-33 is a member of the IL-1 family of cytokines with dual function which either activates cells via the IL-33 receptor in a paracrine fashion or translocates to the nucleus to regulate gene transcription in an intracrine manner. We show that full length murine IL-33 is active as a cytokine and that it is not processed by caspase I to mature IL-33 but instead cleaved by caspase 3 at aa175 to yield two products which are both unable to bind to the IL-33 receptor. Full length IL-33 and its N-terminal caspase 3 breakdown product, however, translocate to the nucleus. Finally, bioactive IL-33 is not released by cells constitutively or after activation. This suggests that IL-33 is not a classical cytokine but exerts its function in the nucleus of intact cells and only activates others cells via its receptor as an alarm mediator after destruction of the producing cell. (c) 2009 Elsevier Inc. All rights reserved.