Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
J Immunol. 2009 Dec 15;183(12):7890-7. doi: 10.4049/jimmunol.0802449.
In addition to IL-1 and IL-18, IL-33 was recently identified as a member of the IL-1 cytokine family. rIL-33 can promote production of Th2-type cytokines by Th2 cells and mast cells in vitro. Administration of rIL-33 to mice results in increases in IgE secretion and eosinophilic inflammation. However, the precise immune cell source of IL-33 remains unclear. Moreover, although recombinant pro-IL-33 is cleaved by recombinant caspase-1 in vitro, as are pro-IL-1beta and pro-IL-18, the involvement of caspase-1 in pro-IL-33 cleavage remains controversial. In this study, we show that mouse peritoneal macrophages, but not splenic dendritic cells, produced IL-33 upon stimulation with LPS. Likewise, mouse bone marrow cell-derived cultured mast cells also produced a small, but significant amount of IL-33 via FcepsilonRI cross-linking, but not in response to stimulation with LPS. To our surprise, IL-33 release was found even in caspase-1-deficient, caspase-8 inhibitor-treated, and calpain inhibitor-treated macrophages. These observations suggest that caspase-1-, caspase-8-, and calpain-independent IL-33 production by macrophages and/or mast cells may contribute to the pathogenesis of Th2-type allergic inflammation.
除了 IL-1 和 IL-18，IL-33 最近被鉴定为 IL-1 细胞因子家族的一员。rIL-33 可以在体外促进 Th2 细胞和肥大细胞产生 Th2 型细胞因子。rIL-33 给药于小鼠导致 IgE 分泌和嗜酸性粒细胞炎症增加。然而，IL-33 的精确免疫细胞来源仍不清楚。此外，尽管重组 pro-IL-33 在体外被重组 caspase-1 切割，就像 pro-IL-1beta 和 pro-IL-18 一样，但 caspase-1 在 pro-IL-33 切割中的参与仍然存在争议。在这项研究中，我们表明，小鼠腹腔巨噬细胞在受到 LPS 刺激时会产生 IL-33，但脾树突状细胞不会。同样，小鼠骨髓细胞来源的培养肥大细胞也通过 FcepsilonRI 交联产生少量但显著的 IL-33，但对 LPS 刺激没有反应。令我们惊讶的是，甚至在 caspase-1 缺陷型、caspase-8 抑制剂处理和钙蛋白酶抑制剂处理的巨噬细胞中也发现了 IL-33 释放。这些观察结果表明，巨噬细胞和/或肥大细胞中 caspase-1、caspase-8 和钙蛋白酶非依赖性的 IL-33 产生可能有助于 Th2 型过敏炎症的发病机制。
