Involvement of IL-32 in activation-induced cell death in T cells
Involvement of IL-32 in activation-induced cell death in T cells
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DOI：
10.1093/intimm/dxh339
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发表时间：
2006-02-01
影响因子：
4.4
通讯作者：
Izuhara, K
中科院分区：
文献类型：
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作者：
Goda, C;Kanaji, T;Izuhara, K
NK细胞转录本4(NK4)，现在被称为IL-32，最初被鉴定为一种在激活的NK细胞中表达增加的转录本。最近的研究表明，在IL-18、IL-1β、干扰素-γ和IL-12等炎性细胞因子的刺激下，NK4可由多种细胞分泌。此外，NK4还可诱导单核细胞产生肿瘤坏死因子、巨噬细胞炎性蛋白(MIP)-2和IL-8，提示该因子可能参与了炎症反应。基于这些发现，NK4被更名为IL-32。然而，IL-32对其他类型细胞的生物学活性仍未确定。此外，IL-32是从细胞外作用于细胞还是从细胞内作用于细胞仍存在争议。在本文中，我们首次报道了IL-32在激活的T细胞和NK细胞中的表达上调，并且IL-32β是激活的T细胞中主要的表达亚型。IL-32在T细胞中特异性表达，并增强IL-32诱导的T细胞凋亡，而下调IL-32可使HeLa细胞免于凋亡。上清液中存在的IL-32可能来源于凋亡细胞的胞浆。这些结果有力地表明，IL-32可能通过其细胞内作用参与了T细胞活化诱导的细胞死亡。我们目前的发现扩大了我们对IL-32生物学功能的理解，并认为IL-32可能不仅从外部而且从内部作用于细胞。
NK cell transcript 4 (NK4), now denoted as IL-32, was originally identified as a transcript whose expression was increased in activated NK cells. It has been very recently demonstrated that NK4 is secreted from several cells upon the stimulation of some inflammatory cytokines such as IL-18, IL-1 beta, IFN-gamma and IL-12. Furthermore, NK4 induces production of tumor necrosis factor, macrophage inflammatory protein (MIP)-2 and IL-8 in monocytic cell lines, indicating that this factor would be involved in the inflammatory responses. Based on these findings, NK4 was renamed IL-32. However, the biological activities of IL-32 on other cell types remained undetermined. Furthermore, it was still argued whether IL-32 acts on cells from outside or inside the cells. In this article, we first report that expression of IL-32 was up-regulated in activated T cells and NK cells, and that IL-32 beta was the predominantly expressed isoform in activated T cells. IL-32 was specifically expressed in T cells undergoing apoptosis and enforced expression of IL-32-induced apoptosis, whereas its down-regulation rescued the cells from apoptosis in HeLa cells. IL-32 existing in the supernatant would be derived from the cytoplasm of apoptotic cells. These results strongly indicated that IL-32 would be involved in activation-induced cell death in T cells, probably via its intracellular actions. Our present findings expand our understanding of the biological function of IL-32 and argue that IL-32 may act on cells, not only from the outside but also from the inside.