A Novel CC-Chemokine Receptor 3 Antagonist, Ki19003, Inhibits Airway Eosinophilia and Subepithelial/Peribronchial Fibrosis Induced by Repeated Antigen Challenge in Mice

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概要

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• CC-chemokine receptor 3 (CCR3) is a chemokine receptor for which major ligands, CC-chemokine ligand (CCL) 11, CCL24, and CCL26, are known to be involved in chemotaxis for eosinophils. In the present study, we evaluated the effect of a low molecular weight CCR3-receptor antagonist, Ki19003 (4-[[5-(2,4-dichlorobenzylureido)pentyl][1-(4-chlorophenyl)ethyl]amino]butanoic acid), on airway remodeling in a mouse model of allergic asthma. BALB/c mice were sensitized twice by intraperitoneal injection of ovalbumin (OA) and exposed daily to 1% OA for 3 weeks. Twenty-four hours after the final antigen challenge, bronchoalveolar lavage and histological examinations were carried out. Ki19003 clearly inhibited antigen-induced increase in the number of eosinophils in bronchoalveolar lavage fluid (BALF), but did not affect the number of other cell types examined in this study. Ki19003 also inhibited the increased production of transforming growth factor-β1 in BALF and the amount of hydroxyproline in the lungs in a dose-dependent manner. Furthermore, Ki19003 significantly attenuated allergen-induced subepithelial and peribronchial fibrosis. These findings indicate that CCR3 antagonism prevents not only the infiltration of eosinophils into the airways but also the development of allergen-induced subepithelial and peribronchial fibrosis. Therefore, a CCR3 antagonist may be useful in the treatment of airway remodeling, especially subepithelial and peribronchial fibrosis, in allergic asthma.

• 社団法人 日本薬理学会の論文

著者

• TANAKA Hiroyuki

  Laboratory of Marine Biotechnology and Microbiology, Graduate School of Fisheries Sciences, Hokkaido

• YOSHIE Osamu

  Department of Microbiology, Kinki University School of Medicine

• ISHIZAKI Masayuki

  Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University

• KAJIWARA Daisuke

  Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University

• INAGAKI Naoki

  Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University

• NAGAI Hiroichi

  Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University

• Takeda H

  Department Of Pharmacology Gifu Pharmaceutical University

• Komai Masato

  Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Japan

• Nagao Koichi

  Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Japan

• Miura Toru

  Pharmacological Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., Japan

• Ohashi Hiroshi

  Pharmacological Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., Japan

• Haba Tomoko

  Pharmacological Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., Japan

• Kawakami Kazuki

  Pharmacological Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., Japan

• Sawa Eiji

  Pharmacological Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., Japan

• Inagaki Naoki

  Laboratory Of Pharmacology Department Of Bioactive Molecules Gifu Pharmaceutical University

• Kajiwara Daisuke

  Laboratory Of Pharmacology Department Of Bioactive Molecules Gifu Pharmaceutical University

• Ishizaki Masayuki

  Laboratory Of Pharmacology Department Of Bioactive Molecules Gifu Pharmaceutical University

• Kimata Masahiro

  岐阜薬科大学 薬理学

• Sawa Eiji

  Pharmaceutical Research Laboratory Kirin Brewery Co. Ltd.

• Nagai Hiroichi

  Laboratory Of Clinical Pharmacology Gifu Pharmaceutical University

• Kimata Masahiro

  Department Of Pharmacology Gifu Pharmaceutical University

• Yoshie Osamu

  Department Of Cancer Research Fuji Gotemba Research Laboratories Chugai And Pharmaceutical Co

• Ohashi Hiroshi

  Pharmaceutical Research Laboratory Kirin Brewery Co. Ltd

• Miura Toru

  Pharmaceutical Development Laboratory And Pharmaceutical Research Laboratory Kirin Brewery Co. Ltd.

• Yoshie Osamu

  Department Of Bacteriology Kinki University School Of Medicine

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