Protease allergens induce the expression of IL-25 via Erk and p38 MAPK pathway.
Protease allergens induce the expression of IL-25 via Erk and p38 MAPK pathway.
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DOI：
10.3346/jkms.2010.25.6.829
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发表时间：
2010-06
影响因子：
4.5
通讯作者：
Dong C
中科院分区：
文献类型：
--
作者：
Yu HS;Angkasekwinai P;Chang SH;Chung Y;Dong C
包括哮喘在内的过敏性疾病的特征在于辅助性T细胞2型（Th 2）细胞介导的炎症，以及嗜酸性粒细胞的组织浸润。在这项研究中，我们证明，多种蛋白酶过敏原，包括木瓜蛋白酶和DerP 1，有效地诱导白细胞介素（IL）-25和胸腺基质淋巴细胞生成素（TSLP）基因的表达，这种现象是依赖于这些过敏原的蛋白酶活性。经木瓜蛋白酶处理后，支气管肺泡灌洗液（BAL）中IL-25细胞因子水平也显著升高。此外，与仅OVA治疗组相比，Th 2细胞因子的水平显著增加。各种蛋白酶过敏原触发小鼠肺上皮细胞（MLE 12）和原代小鼠肺上皮细胞中IL-25和TSLP mRNA的表达，这些作用被木瓜蛋白酶的蛋白酶活性失活抑制。过敏原木瓜蛋白酶激活ErK和p38 MAP通路;抑制这些通路（但不抑制NFκB或PI-3激酶通路）会削弱蛋白酶对IL-25和TSLP表达的诱导。在这项研究中，我们证明，蛋白酶过敏原诱导IL-25和TSLP通过MAP激酶信号通路，和他们的蛋白酶活性是必不可少的这一途径。
Allergic diseases, including asthma, are characterized by T helper type 2 (Th2) cell-mediated inflammations, coupled with tissue infiltration by eosinophils. In this study, we demonstrate that multiple protease allergens, including papain and DerP1, efficiently induce interleukin (IL)-25 and thymic stromal lymphopoietin (TSLP) gene expression, and this phenomenon is dependent on the protease activities of these allergens. The IL-25 cytokine level in bronchial alveolar lavage (BAL) was also profoundly and significantly increased after treatment with papain. Additionally, the levels of Th2 cytokines were significantly increased, as compared to those in the OVA-only treatment group. The various protease allergens triggered the expression of IL-25 and TSLP mRNA in mouse lung epithelial cells (MLE12) and primary mouse lung epithelial cells; these effects were inhibited by the deactivation of the protease activity of papain. The allergen papain activates the ErK and p38 MAP pathways; the inhibition of these pathways, but not the NFκB or PI-3 kinase pathways, impairs the induction of IL-25 and TSLP expression by proteases. In this study, we demonstrate that the protease allergens induce IL-25 and TSLP via the MAP kinase signal pathways, and their protease activities are essential to this pathway.
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影响因子：
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