IL-33 induces IL-13 production by mouse mast cells independently of IgE-FcepsilonRI signals.

IL-33 induces IL-13 production by mouse mast cells independently of IgE-FcepsilonRI signals.
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DOI:
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发表时间:
2007
影响因子:
5.5
通讯作者:
L. Ho;T. Ohno;K. Oboki;Naoki Kajiwara;H. Suto;M. Iikura;Y. Okayama;S. Akira;H. Saito;S. G
L. Ho;T. Ohno;K. Oboki;Naoki Kajiwara;H. Suto;M. Iikura;Y. Okayama;S. Akira;H. Saito;S. G
中科院分区:
医学3区
文献类型:
--
作者:
L. Ho;T. Ohno;K. Oboki;Naoki Kajiwara;H. Suto;M. Iikura;Y. Okayama;S. Akira;H. Saito;S. G

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IL-1相关分子IL-1和IL-18可促进IgE/抗原-Fc ε RI刺激的小鼠肥大细胞产生Th 2细胞因子。另一种IL-1相关分子IL-33最近被鉴定为T1/ST 2的配体。虽然小鼠肥大细胞组成型表达ST 2,IL-33对肥大细胞功能的影响知之甚少。我们发现,IL-33,而不是IL-1 β或IL-18,诱导IL-13和IL-6产生的小鼠骨髓来源的,培养的肥大细胞(BMCCs)独立于IgE。在与无特异性抗原的强细胞因子能SPE-7 IgE孵育的BMCCs中,IL-33、IL-1 β和IL-18均促进IL-13和IL-6的产生,但IL-33的作用比IL-1 β或IL-18更强。IL-33通过MyD 88依赖性但含有Toll/IL-1 R结构域的接头诱导IFN-β非依赖性途径促进细胞因子产生。相比之下,IL-33既不诱导也不增强肥大细胞脱粒。在200 ng/ml时,IL-33在不存在IgE的情况下延长肥大细胞存活,在存在SPE-7 IgE的情况下损害存活,而在100 ng/ml时,IL-33在不存在IgE的情况下对肥大细胞存活没有影响,在存在IgE的情况下降低肥大细胞存活。这些观察结果表明IL-33在肥大细胞和Th 2细胞相关的免疫应答和疾病中的潜在作用。
The IL-1-related molecules, IL-1 and IL-18, can promote Th2 cytokine production by IgE/antigen-FcepsilonRI-stimulated mouse mast cells. Another IL-1-related molecule, IL-33, was identified recently as a ligand for T1/ST2. Although mouse mast cells constitutively express ST2, the effects of IL-33 on mast cell function are poorly understood. We found that IL-33, but not IL-1beta or IL-18, induced IL-13 and IL-6 production by mouse bone marrow-derived, cultured mast cells (BMCMCs) independently of IgE. In BMCMCs incubated with the potently cytokinergic SPE-7 IgE without specific antigen, IL-33, IL-1beta, and IL-18 each promoted IL-13 and IL-6 production, but the effects of IL-33 were more potent than those of IL-1beta or IL-18. IL-33 promoted cytokine production via a MyD88-dependent but Toll/IL-1R domain-containing adaptor-inducing IFN-beta-independent pathway. By contrast, IL-33 neither induced nor enhanced mast cell degranulation. At 200 ng/ml, IL-33 prolonged mast cell survival in the absence of IgE and impaired survival in the presence of SPE-7 IgE, whereas at 100 ng/ml, IL-33 had no effect on mast cell survival in the absence of IgE and reduced mast cell survival in the presence of IgE. These observations suggest potential roles for IL-33 in mast cell- and Th2 cytokine-associated immune responses and disorders.