| Budget Amount *help |
¥3,910,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
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.
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