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1 Shin Nippon Biomedical Laboratories, Tokyo, Ishikawa, Japan; Department of Public Health, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Okayama Prefecture, Japan
2 Third Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Tokushima, Tokushima, Japan
3 Department of Environmental and Preventive Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan
4 Department of Public Health, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Okayama, Japan
5 Department of Viral Infection and International Health, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa prefecture, Japan
6 Division of Morphological Analysis, Faculty of Medicine, Department of Anatomy, Biology and Medicine, Oita University, Yufu, Japan
* To whom correspondence should be addressed. E-mail: kogino{at}md.okayama-u.ac.jp.
Changes in the expression of arginase and their association with nitrosative stress were investigated using an asthmatic model previously established in NC/Nga mice with mite extract. Mite crude extract (100 µg/day) from Dermatophagoides farinae (Df) was administered intranasally for 5 consecutive days (day 0-4) and a single challenge was performed on day 11. On day 12, up-regulation of the mRNA expression of inducible types of nitric oxide synthase (iNOS) and increases in immunohistochemical staining for iNOS and nitrotyrosine were observed. However, the level of NOx (nitrite + nitrate) was unchanged. An increase in enzymatic activity, up-regulation of mRNA expression, and immunostaining for arginase I were detected in the lung tissue and serum. Moreover, increases in both arginase I and II were revealed by immunoblotting. Goblet cell hyperplasia in bronchial epithelial cells and increasing collagen synthesis around the bronchus were also observed. These results suggested that an increase in arginase may lead to decreased availability of arginine for NOS, and may contribute to the remodeling of the lung.
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