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

目的：IκBζ-/-小鼠被报道为过敏性皮炎。目的：探讨IκBζ在IκBζ-/-小鼠眼表炎症和皮炎发病机制中的作用。方法：建立无个体差异的BALB/c背景IκBζ-/-小鼠，建立不能产生Th2型细胞因子的IκBζ/STAT6双基因敲除小鼠，并进行光镜、组织学和免疫化学研究。结果：IκBζ-/-小鼠眼表及口周皮肤均表现出严重的炎症表型，IκBζ-/-小鼠眼表及口周皮肤表现为严重的炎症表型。口腔周围皮肤的炎性浸润物主要由CD4和CD8阳性细胞组成，结膜中主要检测到CD4和CD45R/B220阳性细胞。在眼睑和口周皮肤组织中，IL-17a和Th1和Th2细胞因子的表达增加，但CCL11的表达不增加。IκBζ-/-和IκBζ-I+小鼠发病前及发病后0~4周和5~9周血清总IgE水平无显著差异。IκBζ/STAT6WKO小鼠的炎症反应与IκBζ-/-小鼠相同或略重。结论：免疫球蛋白E和STAT6不参与导致IκBζ-/-小鼠眼表和口周皮肤炎症的免疫病理反应。IκBζ-/-小鼠可能是一种适合史蒂文斯-约翰逊综合征的动物模型，但不是特应性皮炎的模型。

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.