IL-33 can promote survival, adhesion and cytokine production in human mast cells
IL-33 can promote survival, adhesion and cytokine production in human mast cells
复制标题
DOI：
10.1038/labinvest.3700663
复制
发表时间：
2007-10-01
影响因子：
5
通讯作者：
Nakae, Susumu
中科院分区：
文献类型：
--
作者：
Iikura, Motoyasu;Suto, Hajime;Nakae, Susumu
白细胞介素 - 33是白细胞介素 - 1分子家族中近期被鉴定出的成员，该家族还包括白细胞介素 - 1和白细胞介素 - 18。白细胞介素 - 33与受体T1/ST2/白细胞介素 - 1R4结合，能够促进Th2细胞的细胞因子分泌以及小鼠肥大细胞中核因子 - κB的磷酸化。然而，这些分子，尤其是白细胞介素 - 33在人肥大细胞中的作用却鲜为人知。通过流式细胞术可在人脐带血来源的肥大细胞（HUCBMCs）内检测到白细胞介素 - 1家族分子的受体，特别是白细胞介素 - 1R1、白细胞介素 - 18R和T1/ST2的表达，但在细胞表面几乎检测不到。然而，白细胞介素 - 1β、白细胞介素 - 18或白细胞介素 - 33可诱导未刺激的HUCBMCs中Erk、p38和JNK的磷酸化，白细胞介素 - 33或白细胞介素 - 1β，但不是白细胞介素 - 18，可提高未刺激的HUCBMCs的存活率并促进其与纤连蛋白的黏附。白细胞介素 - 33或白细胞介素 - 1b还可诱导未刺激的HUCBMCs产生白细胞介素 - 8和白细胞介素 - 13，并增强IgE/抗IgE刺激的HUCBMCs中这些细胞因子的产生，但不增强前列腺素D₂（PGD₂）或组胺的分泌。此外，p38丝裂原活化蛋白激酶抑制剂SB203580可显著降低HUCBMCs中白细胞介素 - 33介导的白细胞介素 - 8的产生。与在小鼠肥大细胞中的发现相反，白细胞介素 - 18既不诱导也不增强HUCBMCs中介质PGD₂或组胺的分泌。我们的研究结果确定了白细胞介素 - 33在人肥大细胞中以前未知的功能。其中之一是，白细胞介素 - 33像白细胞介素 - 1b一样，即使在没有Fc εRI聚集刺激的情况下，也能诱导人肥大细胞产生细胞因子。因此，我们的研究结果支持这样一种假设：在过敏性疾病和其他情况下，无论是否存在通过IgE/抗原 - Fc εRI信号对肥大细胞的共刺激，白细胞介素 - 33都可能增强肥大细胞的功能。
IL-33 is a recently identified member of the IL-1 family of molecules, which also includes IL-1 and IL-18. IL- 33 binds to the receptor, T1/ST2/IL-1R4, and can promote cytokine secretion by Th2 cells and NF-kappa B phosphorylation in mouse mast cells. However, the effects of these molecules, especially IL- 33, in human mast cells are poorly understood. Expression of the receptors for IL- 1 family molecules, specifically, IL- 1R1, IL- 18R and T1/ST2, was detectable intracellularly in human umbilical cord blood-derived mast cells (HUCBMCs) by flow cytometry, but was scarcely detectable on the cells' surface. However, IL-1 beta, IL- 18 or IL- 33 induced phosphorylation of Erk, p38 and JNK in naive HUCBMCs, and IL- 33 or IL- 1 beta, but not IL- 18, enhanced the survival of naive HUCBMCs and promoted their adhesion to fibronectin. IL- 33 or IL- 1b also induced IL- 8 and IL- 13 production in naive HUCBMCs, and enhanced production of these cytokines in IgE/anti-IgE-stimulated HUCBMCs, without enhancing secretion of either PGD(2) or histamine. Moreover, IL-33-mediated IL- 8 production by HUCBMCs was markedly reduced by the p38 MAPK inhibitor, SB203580. In contrast to findings with mouse mast cells, IL- 18 neither induced nor enhanced secretion of the mediators PGD(2) or histamine by HUCBMCs. Our findings identify previously unknown functions of IL-33 in human mast cells. One of these is that IL- 33, like IL- 1b, can induce cytokine production in human mast cells even in the absence of stimuli of Fc epsilon RI aggregation. Our findings thus support the hypothesis that IL- 33 may enhance mast cell function in allergic disorders and other settings, either in the presence or absence of co-stimulation of mast cells via IgE/antigen-Fc epsilon RI signals.