[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: Takayuki Tsukuba, Kenji Yamamoto
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 122 Issue 1 Pg. 15-20 (Jul 2003) ISSN: 0015-5691 [Print] Japan
• PMID: 12843568 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• Interleukin-1
• Interleukin-18
• Cathepsin E

Topics

• Animals
• Cathepsin E (deficiency, genetics, physiology)
• Dermatitis, Atopic (etiology)
• Disease Models, Animal
• Humans
• Interleukin-1 (metabolism)
• Interleukin-18 (metabolism)
• Mice
• Mice, Knockout
• Th2 Cells (immunology)