Association of cathepsin E deficiency with development of atopic dermatitis.

Abstract

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-1beta accompanied by a marked increase in IL-4, IL-5, and IgE. The relative rates of degradation of IL-18 and IL-1beta 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-1beta, 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.

• Authors: Takayuki Tsukuba, Kuniaki Okamoto, Yoshiko Okamoto, Michiyo Yanagawa, Keiko Kohmura, Yoshiyuki Yasuda, Hiroshi Uchi, Takeshi Nakahara, Masutaka Furue, Keiko Nakayama, Tomoko Kadowaki, Kenji Yamamoto, Keiichi I Nakayama
• Journal: Journal of biochemistry (J Biochem) Vol. 134 Issue 6 Pg. 893-902 (Dec 2003) ISSN: 0021-924X [Print] England
• PMID: 14769879 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Haptens
• Interleukin-1
• Interleukin-18
• Immunoglobulin E
• Cathepsin E

Topics

• Animals
• Cathepsin E (biosynthesis, blood, deficiency, genetics)
• Cells, Cultured
• Cytokines (biosynthesis)
• Dermatitis, Atopic (enzymology, genetics, immunology)
• Dermatitis, Contact (blood, enzymology, genetics)
• Erythrocytes (enzymology)
• Haptens (toxicity)
• Humans
• Immunoglobulin E (biosynthesis)
• Interleukin-1 (antagonists & inhibitors, metabolism)
• Interleukin-18 (antagonists & inhibitors, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Th2 Cells (enzymology, immunology)