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Analysis of NF-κ B/Iκ B signaling pathway on Iκ Bζ deficient mice

Iκ Bζ缺陷小鼠NF-κ B/Iκ B信号通路分析

基本信息

批准号：
18591256
负责人：
UEDA Eiichiro
金额：
$ 2.5万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591256/
关键词：
IκBζ innate immunity dermatitis

项目摘要

Purpose: IκBζ-/- mice were reported to be affected by allergic dermatitis. To analyze the pathophysiological role of IκBζ; and to address the functional relevance of Th2-mediated immune responses in the development of ocular surface inflammation and dermatitis by IκBζ-/- mice.Methods: We established Balb/c background IκBζ-/- mice without individual differences, created IκBζ/Stat6 double-knock-out (WKO) mice unable to produce Th2 cytokine, and performed microscopic-, histological-, and immunochemical studies. In IκBζ-/- mice we examined the serum IgE levels by ELISA and used quantitative PCR to study the gene expression of IFN-γ, IL4, IL10, TNFα, IL6, IL17α, and CCL11 in eyelid tissue.Results: IκBζ,-/- mice exhibited a severe inflammatory phenotype on the ocular surface and perioral skin. The inflammatory infiltrates in the perioral skin consisted primarily of CD4- and CD8-positive cells; in the conjunctiva we mainly detected CD4- and CD45R/B220-positive cells. In eyelid and perioral skin tissue the expression of IL-17a and of Th1 and Th2 cytokines, but not of CCL11, was augmented. IκBζ-/- and IκBζ-I+ mice did not differ significantly in their serum total IgE levels before- and 0-4- and 5-9 weeks after disease onset. IκBζ/Stat6 WKO mice elicited the same or a little more severe inflammation than that of IκBζ-/- mice.Conclusion: IgE and Stat6 are not responsible for the immune-pathological response leading to the development of ocular surface and perioral skin inflammation in IκBζ-/- mice. IκBζ-/- mice might be a suitable model for Stevens-Johnson syndrome, but not atopic dermatitis.

目的：研究IκB B-/-小鼠的变应性皮炎。分析IκB T的病理生理学作用;并通过IκB T-/-小鼠阐明Th 2介导的免疫应答在眼表炎症和皮炎发展中的功能相关性。我们建立了无个体差异的BalB/c背景IκB κ-/-小鼠，建立了不能产生Th 2细胞因子的IκB κ/Stat 6双敲除（WKO）小鼠，并进行了显微镜、组织学、和免疫化学研究。结果：I κB-/-小鼠眼表和口周皮肤出现严重的炎症表型; I κ B B-/-小鼠眼睑组织中IFN-γ、IL 4、IL 10、TNFα、IL 6、IL 17 α和CCL 11基因表达水平明显高于IκB B-/-小鼠。口周皮肤的炎性浸润主要由CD 4-和CD 8-阳性细胞组成;在结膜中，我们主要检测到CD 4-和CD 45 R/B220-阳性细胞。在眼睑和口周皮肤组织中，IL-17 a和Th 1和Th 2细胞因子的表达增加，但CCL 11的表达没有增加。IκB-/-和IκB-I+小鼠在发病前、发病后0-4周和5-9周的血清总IgE水平无显著差异。结论：IgE和Stat 6在I κ B β-/-小鼠眼表和口周皮肤炎症的发生中不起作用。IκB κ-/-小鼠可能是Stevens-Johnson综合征的合适模型，但不是特应性皮炎的合适模型。