Pulmonary Suppressor of Cytokine Signaling-1 Induced by IL-13 Regulates Allergic Asthma Phenotype
Pulmonary Suppressor of Cytokine Signaling-1 Induced by IL-13 Regulates Allergic Asthma Phenotype
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DOI：
10.1164/rccm.200806-992oc
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发表时间：
2009-06-01
影响因子：
24.7
通讯作者：
Inoue, Hiromasa
中科院分区：
文献类型：
--
作者：
Fukuyama, Satoru;Nakano, Takako;Inoue, Hiromasa
原理：Th 2细胞因子在过敏性疾病中起重要作用。这些细胞因子激活信号转导途径，包括Janus激酶/信号转导子和转录激活子（STAT）信号传导。尽管细胞因子信号转导抑制因子（SOCS）家族蛋白是Janus激酶/STAT信号通路的负调节因子，在免疫应答过程中参与辅助性T细胞的分化，但SOCS蛋白在靶器官结构细胞中的作用在变态反应中尚未阐明。我们使用IL-13和卵清蛋白（OVA）诱导的过敏性气道疾病的小鼠模型。哮喘患者的气道平滑肌细胞培养。测量和主要结果：IL-13的管理不仅诱导气道反应，但也SOCS 1在局部炎症部位的表达。上调的SOCS 1显著抑制IL-13依赖性STAT 6活化和嗜酸性粒细胞趋化因子表达，随后下调IL-13诱导的气道炎症反应。SOCS 1的失活在IL-13治疗后诱导气道高反应性，即使在低反应性CS 7 BL/6背景小鼠中也是如此。在OVA诱导的过敏性气道疾病模型中，过敏原暴露上调局部SOCS 1表达，气道中SOCS 1的诱导减弱过敏原诱导的气道反应。在过敏性气道疾病模型中，IL-13的失活抑制SOCS 1诱导。有趣的是，哮喘患者的气道平滑肌细胞在IL-13刺激后SOCS 1的上调受损。结论：IL-13在气道结构细胞中诱导SOCS 1对负控制过敏性气道疾病至关重要。
Rationale: Th2 cytokines play an important role in allergic diseases. These cytokines activate signal transduction pathways, including Janus kinase/signal transducer and activator of transcription (STAT) signaling. Although the suppressor of cytokine signaling (SOCS) family protein, a negative regulator of the Janus kinase/STAT signaling pathway, contributes to helper T cell differentiation during immune responses, the role of SOCS proteins within the structural cells of a target organ has not been clarified in allergy.Objectives: To study the local function of SOCS in the development of asthma.Methods: We used mouse models of IL-13- and ovalbumin (OVA)induced allergic airway disease. Airway smooth muscle cells were cultured from patients with asthma.Measurements and Main Results: The administration of IL-13 induced not only airway responses but also SOCS1 expression at the local inflammatory site. The up-regulated SOCS1 markedly suppressed IL-13-dependent STAT6 activation and eotaxin expression and subsequently down-regulated IL-13-induced airway inflammatory responses. The inactivation of SOCS1 induced airway hyperresponsiveness after IL-13 treatment even in hyporesponsive CS7BL/6 background mice. In an OVA-induced model of allergic airway disease, allergen exposure up-regulated local SOCS1 expression, and the induction of SOCS1 in the airways attenuated allergen-induced airway responses. Inactivation of IL-13 inhibited SOCS1 induction in a model of allergic airway disease. Interestingly, airway smooth muscle cells from individuals with asthma had impaired upregulation of SOCS1 after IL-13 stimulation.Conclusions: SOCS1 induction by IL-13 in airway structural cells is critical to negatively control allergic airway disease.