Direct inhibition of arginase attenuated airway allergic reactions and inflammation in a Dermatophagoides farinae-induced NC/Nga mouse model.

Abstract

The expression of arginase I has been a focus of research into the pathogenesis of experimental asthma, because arginase deprives nitric oxide synthase (NOS) of arginine and therefore participates in the attenuation of bronchodilators such as nitric oxide (NO). The present study used an intranasal mite-induced NC/Nga mouse model of asthma to investigate the contribution of arginase to the asthma pathogenesis, using an arginase inhibitor, N(omega)-hydroxy-nor-l-arginine (nor-NOHA). The treatment with nor-NOHA inhibited the increase in airway hyperresponsiveness (AHR) and the number of eosinophils in bronchoalveolar lavage fluid. NOx levels in the lung were elevated despite suppressed NOS2 mRNA expression. Accompanied by the attenuated activity of arginase, the expression of arginase I at both the mRNA and protein level was downregulated. The levels of mRNA for T helper 2 cytokines such as IL-4, IL-5, and IL-13, and for chemotactants such as eotaxin-1 and eotaxin-2, were reduced. Moreover, the accumulation of inflammatory cells and the ratio of goblet cells in the bronchiole were decreased. The study concluded that the depletion of NO caused by arginase contributes to AHR and inflammation, and direct administration of an arginase inhibitor to the airway may be beneficial and could be of use in treating asthma due to its anti-inflammatory and airway-relaxing effects, although it is not clear whether the anti-inflammatory effect is direct or indirect.

• Authors: Noriko Takahashi, Keiki Ogino, Kei Takemoto, Seiji Hamanishi, Da-Hong Wang, Tomoko Takigawa, Masafumi Shibamori, Hironobu Ishiyama, Yoshihisa Fujikura
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 299 Issue 1 Pg. L17-24 (Jul 2010) ISSN: 1522-1504 [Electronic] United States
• PMID: 20382750 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Antigens, Dermatophagoides
• Cytokines
• Enzyme Inhibitors
• Isoenzymes
• N(omega)-hydroxynorarginine
• Nitric Oxide
• 3-nitrotyrosine
• Tyrosine
• Arginine
• Nitric Oxide Synthase
• Arginase

Topics

• Allergens (immunology)
• Animals
• Antigens, Dermatophagoides (immunology)
• Arginase (antagonists & inhibitors, genetics)
• Arginine (analogs & derivatives, pharmacology, therapeutic use)
• Asthma (drug therapy, immunology)
• Bronchial Hyperreactivity (drug therapy, immunology)
• Cytokines (genetics, immunology)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Humans
• Isoenzymes (genetics, metabolism)
• Male
• Mice
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (genetics, metabolism)
• Tyrosine (analogs & derivatives, metabolism)