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Am J Physiol Lung Cell Mol Physiol 293: L1419-L1426, 2007. First published September 21, 2007; doi:10.1152/ajplung.00418.2006
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Transiently, paralleled upregulation of arginase and nitric oxide synthase and the effect of both enzymes on the pathology of asthma

Kei Takemoto,1,2 Keiki Ogino,2 Masafumi Shibamori,3 Toshikazu Gondo,4 Yoshiaki Hitomi,5 Tomoko Takigawa,2 Da-Hong Wang,2 Jiro Takaki,2 Hiroshi Ichimura,6 Yoshihisa Fujikura,7 and Hironobu Ishiyama3

1Shin Nippon Biomedical Laboratories, Tokyo; 2Department of Public Health, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama; 3Third Institute of New Drug Discovery, Otsuka Pharmaceutical Company Limited, Tokushima; 4Department of Surgical Pathology, Yamaguchi University Hospital, Yamaguchi; Departments of 5Environmental and Preventive Medicine and 6Viral Infection and International Health, Graduate School of Medical Science, Kanazawa University, Kanazawa; and 7Division of Morphological Analysis, Faculty of Medicine, Department of Anatomy, Biology, and Medicine, Oita University, Oita City, Japan

Submitted 19 October 2006 ; accepted in final form 4 September 2007

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 was administered intranasally for 5 consecutive days (day 0–4), and a single challenge was performed on day 11. On day 12, upregulation 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 nitrite + nitrate was unchanged. An increase in enzymatic activity, upregulation of mRNA expression, and immunostaining for arginase I was 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 nitric oxide synthase and may contribute to the remodeling of the lung.

NC/Nga; mite; reactive nitrogen species; airway remodeling



Address for reprint requests and other correspondence: K. Ogino, Dept. of Public Health, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama Univ., 2-5-1, Shikata, Okayama 700-8558, Japan (e-mail: kogino{at}md.okayama-u.ac.jp)




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