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J. Biochem, 2003, Vol. 134, No. 6 893-902
© 2003 Japanese Biochemical Society

BIOCHEMISTRY

Association of Cathepsin E Deficiency with Development of Atopic Dermatitis

Takayuki Tsukuba*,1, Kuniaki Okamoto*,1, Yoshiko Okamoto2, Michiyo Yanagawa1, Keiko Kohmura1, Yoshiyuki Yasuda1, Hiroshi Uchi3, Takeshi Nakahara3, Masutaka Furue3, Keiko Nakayama4, Tomoko Kadowaki1, Kenji Yamamoto§,1 and Keiichi I. Nakayama4

1 Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582; 2 Department of Biochemistry, Daiichi University College of Pharmaceutical Sciences Fukuoka 815-8511; 3 Department of Dermatology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582; and 4 Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582

Atopic dermatitis (AD) is a pruritic inflammatory skin diseases associated with a family history of atropy. Here we show that mice lacking the endolysosomal aspartic proteinase cathepsin E spontaneously develop skin lesions similar to those of humans with AD when reared under conventional conditions but not under specific pathogen-free conditions. These mice showed the increase in the ratio of CD4+/CD8+ T cells, the strong polarization of naïve T cells to T helper 2 cells, and the systemic accumulation of IL-18 and IL-1ß accompanied by a marked increase in IL-4, IL-5, and IgE. The relative rates of degradation of IL-18 and IL-1ß were significantly lower in cathepsin E–deficient mice than wild-type mice. These results strongly suggest that the development of AD in cathepsin E-deficient mice is initiated by systemic accumulation of IL-18 and IL-1ß, mainly due to their reduced turnover rates. In addition, the reduced expression of cathepsin E was also observed in erythrocytes of both humans with AD and the AD mouse model NC/Nga. Cathepsin E deficiency might thus be responsible for the induction of AD in humans and mice.

* T.T. and K.O. contributed equally to this study.

§ To whom correspondence should be addressed. Tel: +81-92-642-6337, Fax: +81-92-642-6342, E-mail: kyama{at}dent.kyushu-u.ac.jp


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