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A more recent version of this article appeared on August 1, 2008
(Investigative Ophthalmology and Visual Science. )
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-1691

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Article

Stat6-independent tissue inflammation occurs selectively on the ocular surface and perioral skin of I{kappa}B{zeta}-/- mice

Mayumi Ueta 1*, Junji Hamuro 1, Eiichiro Ueda 2, Norito Katoh 2, Masahiro Yamamoto 3, Kiyoshi Takeda 3, Shizuo Akira 4, and Shigeru Kinoshita 1

1 Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
2 Department of Dermatology,, Kyoto Prefectural University of Medicine, Kyoto, Japan
3 Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
4 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

* To whom correspondence should be addressed. E-mail: mueta{at}ophth.kpu-m.ac.jp.


   Abstract

Purpose: I{kappa}B{zeta}-/- mice were reported to be affected by allergic dermatitis. To analyze the pathophysiological role of I{kappa}B{zeta} and to address the functional relevance of Th2-mediated immune responses in the development of ocular surface inflammation and dermatitis by I{kappa}B{zeta}-/- mice. Methods: We established Balb/c background I{kappa}B{zeta}-/- mice without individual differences, created I{kappa}B{zeta}/Stat6 double-knock-out (WKO) mice unable to produce Th2 cytokine, and performed microscopic-, histological-, and immunochemical studies. In I{kappa}B{zeta}-/- mice we examined the serum IgE levels by ELISA and used quantitative PCR to study the gene expression of IFN-{gamma}, IL4, IL10, TNF{alpha}, IL6, IL17{alpha}, and CCL11 in eyelid tissue. Results: I{kappa}B{zeta}-/- 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-17{alpha} and of Th1 and Th2 cytokines, but not of CCL11, was augmented. I{kappa}B{zeta}-/- and I{kappa}B{zeta}-/+ mice did not differ significantly in their serum total IgE levels before- and 0-4- and 5-9 weeks after disease onset. I{kappa}B{zeta}/Stat6 WKO mice elicited the same or a little more severe inflammation than that of I{kappa}B{zeta}-/- 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 I{kappa}B{zeta}-/- mice. I{kappa}B{zeta}-/- mice might be a suitable model for Stevens-Johnson syndrome (SJS), but not atopic dermatitis.

Key Words: I{kappa}B{zeta}-/- mice, ocular surface inflammation, Stevens-Johnson syndrome, dermatitis, Stat6







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