Role of IL/25 in the regulation of allergic airway inflammation

IL/25在过敏性气道炎症调节中的作用

基本信息

批准号：
15590797
负责人：
IWAMOTO Itsuo
金额：
$ 2.24万
依托单位：
CHIBA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590797/
关键词：
IL-25 Mast cells IL-17 Eosinophils Th2 cells 好酸球 Th2細胞

项目摘要

Recently, cytokines homologous to IL-17 have been identified by database searching. Five new family members have been identified, namely IL-17B,IL-17C,IL-17D,IL-17E/IL-25,and IL-17F, in which these molecules possess 18-30% homology to IL-17. Among IL-17 family cytokines, it has been shown that the in vivo and in vitro biological activities of IL-25 are markedly different from those described for IL-17 and other IL-17 family cytokines. The expression of IL-25 results in the expansion of eosinophils through the production of IL-5 from an unidentified non-T cell population, whereas other IL-17 family cytokines induce the expansion of neutrophils. In addition, IL-25 induces elevated gene expression of IL-4 and IL-13 in multiple tissues and the resultant Th2-type immune responses, including increased serum IgE levels and pathological changes with eosinophilic infiltrates.In the present study, we first show that mast cells are also potent IL-25-producing cells. We found that when bone marrow-derived mast cells(BMMCs) were stimulated by IgE cross-linking, IL-25 mRNA was induced within 30 min in a calcineurin-dependent manner and the levels of IL-25 mRNA were comparable to that of activated Th2 cells. Production of IL-25 by mast cells was also detected at protein levels by immunoblotting.We also investigated the role of IL-25 in allergic airway inflammation. We found that IL-25 mRNA was induced in the airways in the sensitized mice upon the inhaled allergen challenge. Moreover, the enforced expression of IL-25 in the lung in CC10-IL-25 transgenic mice resulted in the enhanced antigen-induced airway inflammation. These results suggest that IL-25 is involved in the enhancement of allergic airway inflammation.

最近，通过数据库检索已鉴定出与IL-17同源的细胞因子。已鉴定出五个新的家族成员，即IL-17B、IL-17C、IL-17D、IL-17E/IL-25和IL-17F，其中这些分子与IL-17具有18-30%的同源性。在IL-17家族细胞因子中，IL-25的体内和体外生物活性与IL-17和其他IL-17家族细胞因子的描述显着不同。 IL-25 的表达通过未鉴定的非 T 细胞群产生 IL-5 导致嗜酸性粒细胞扩增，而其他 IL-17 家族细胞因子则诱导中性粒细胞扩增。此外，IL-25诱导多种组织中IL-4和IL-13基因表达升高，以及由此产生的Th2型免疫反应，包括血清IgE水平升高和嗜酸性粒细胞浸润的病理变化。在本研究中，我们首先展示肥大细胞也是有效的 IL-25 产生细胞。我们发现，当骨髓源性肥大细胞（BMMC）受到 IgE 交联刺激时，IL-25 mRNA 在 30 分钟内以钙调磷酸酶依赖性方式被诱导，并且 IL-25 mRNA 的水平与激活的 IL-25 mRNA 水平相当。 Th2细胞。肥大细胞产生的 IL-25 也通过免疫印迹在蛋白质水平上检测到。我们还研究了 IL-25 在过敏性气道炎症中的作用。我们发现，在吸入过敏原后，致敏小鼠的气道中会诱导 IL-25 mRNA 的产生。此外，CC10-IL-25转基因小鼠肺中IL-25的增强表达导致抗原诱导的气道炎症增强。这些结果表明IL-25参与过敏性气道炎症的增强。