Antifibrotic effects of CXCR4 antagonist in bleomycin-induced pulmonary fibrosis in mice

Hideki Makino; Yoshinori Aono; Momoyo Azuma; Masami Kishi; Yuki Yokota; Katsuhiro Kinoshita; Akio Takezaki; Jun Kishi; Hiroshi Kawano; Hirohisa Ogawa; Hisanori Uehara; Keisuke Izumi; Saburo Sone; Yasuhiko Nishioka

doi:10.2152/jmi.60.127

Originals

Antifibrotic effects of CXCR4 antagonist in bleomycin-induced pulmonary fibrosis in mice

Hideki Makino, Yoshinori Aono, Momoyo Azuma, Masami Kishi, Yuki Yokota, Katsuhiro Kinoshita, Akio Takezaki, Jun Kishi, Hiroshi Kawano, Hirohisa Ogawa, Hisanori Uehara, Keisuke Izumi, Saburo Sone, Yasuhiko Nishioka

Author information

Hideki Makino
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, the University of Tokushima Graduate School
Yoshinori Aono
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, the University of Tokushima Graduate School
Momoyo Azuma
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, the University of Tokushima Graduate School
Masami Kishi
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, the University of Tokushima Graduate School
Yuki Yokota
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, the University of Tokushima Graduate School
Katsuhiro Kinoshita
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, the University of Tokushima Graduate School
Akio Takezaki
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, the University of Tokushima Graduate School
Jun Kishi
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, the University of Tokushima Graduate School
Hiroshi Kawano
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, the University of Tokushima Graduate School
Hirohisa Ogawa
Department of Molecular and Environmental Pathology, Institute of Health Biosciences, the University of Tokushima Graduate School
Hisanori Uehara
Department of Molecular and Environmental Pathology, Institute of Health Biosciences, the University of Tokushima Graduate School
Keisuke Izumi
Department of Molecular and Environmental Pathology, Institute of Health Biosciences, the University of Tokushima Graduate School
Saburo Sone
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, the University of Tokushima Graduate School
Yasuhiko Nishioka
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, the University of Tokushima Graduate School

Keywords: pulmonary fibrosis, fibrocyte, CXCR4, CXCL12, AMD3100

JOURNAL FREE ACCESS

2013 Volume 60 Issue 1.2 Pages 127-137

DOI https://doi.org/10.2152/jmi.60.127

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Abstract

Circulating fibrocytes had been reported to migrate into the injured lungs, and contribute to fibrogenesis via chemokine-chemokine receptor systems including CXCL12-CXCR4 axis. Here we hypothesized that blockade of CXCR4 might inhibit the migration of fibrocytes to the injured lungs and the subsequent pulmonary fibrosis. To explore the antifibrotic effects of blockade of CXCR4, we used a specific antagonist for CXCR4, AMD3100, in bleomycin-induced pulmonary fibrosis model in mice. Administration of AMD3100 significantly improved the loss of body weight of mice treated with bleomycin, and inhibited the fibrotic lesion in subpleural areas of the lungs. The quantitative analysis demonstrated that treatment with AMD3100 reduced the collagen content and fibrotic score (Aschcroft score) in the lungs. Although AMD3100 did not affect cell classification in bronchoalveolar lavage fluid on day 7, the percentage of lymphocytes was reduced by AMD3100 on day 14. AMD3100 directly inhibited the migration of human fibrocytes in response to CXCL12 in vitro, and reduced the trafficking of fibrocytes into the lungs treated with bleocmycin in vivo. These results suggest that the blockade of CXCR4 might be useful strategy for therapy of patients with pulmonary fibrosis via inhibiting the migration of circulating fibrocytes. J. Med. Invest. 60: 127-137, February, 2013

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