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Chymase inhibitor improves dermatitis in NC/Nga mice
Naohiro Watanabe1, Yoshiaki Tomimori, Kayo Saito
1Department of Tropical Medicine, Jikei University School of Medicine, Tokyo, Japan.
International Archives of Allergy and Immunology
|July 18, 2002
Summary
Mast cell chymase inhibition reduced skin lesions and inflammation in a mouse model of atopic dermatitis (AD). This suggests chymase plays a role in AD pathogenesis and that inhibitors could treat this skin disorder.
Area of Science:
- Immunology
- Dermatology
- Pharmacology
Background:
- Mast cell chymase involvement in allergic inflammation is suspected but not fully understood.
- NC/Nga mice exhibit atopic dermatitis-like skin lesions in conventional environments.
Purpose of the Study:
- To investigate the role of mast cell chymase in atopic dermatitis (AD).
- To evaluate the efficacy of a chymase inhibitor (SUN-C8257) in a mouse model of AD.
Main Methods:
- NC/Nga mice were administered SUN-C8257 (150 mg/kg/day) in drinking water.
- Dermatitis severity was assessed on day 35.
- In vitro and in vivo studies used recombinant mouse mast cell protease-4 (mMCP-4).
Main Results:
- SUN-C8257 significantly decreased clinical and histological skin lesion scores.
- The inhibitor reduced inflammatory cell accumulation (eosinophils, mast cells) in lesions.
- mMCP-4 promoted eosinophil migration in vitro and in vivo.
Conclusions:
- Mast cell chymase may contribute to atopic dermatitis pathogenesis.
- SUN-C8257 demonstrated potential as a therapeutic agent for this skin disorder.