title: [Atopic dermatitis and cathepsin E].
abstract: Cathepsin E is an intracellular aspartic proteinase expressed predominantly in immune cells and skin. We show that cathepsin E-deficient mice spontaneously develop atopic dermatitis (AD)-like skin lesions comparable to human AD when kept under conventional circumstances, but not under specific pathogen-free conditions. These mice displayed AD-associated phenotypes including eosinophilia; increased serum IgE, IL-18, and IL-1beta; and enhanced production of Th2 cytokines. Cathepsin E deficiency also resulted in greater decrease of the rate of degradation for serum IL-18 and IL-1beta. Interestingly, cathepsin E levels in blood cells were significantly decreased in AD patients and the AD model NC/Nga mice compared to healthy donors and the control mice, respectively. Our results indicate that deficiency or defective production of cathepsin E strongly induces AD in humans and mice, probably due to the systemic accumulation of IL-18 and IL-1beta, leading to stimulation of Th2 responses, and that cathepsin E-deficient mice are a newly discovered model to analyze pathologic mechanisms of human AD.
authors.affiliation: Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan. tsukuba@dent.kyushu-u.ac.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tsukuba
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D020059:Cathepsin E / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D003876:Dermatitis, Atopic / Q000209:etiology*; D004195:Disease Models, Animal; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology
chemical_list: D007375:Interleukin-1; D020382:Interleukin-18; D020059:Cathepsin E