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Effects of IS-741, a Synthetic Anti-Inflammatory Agent, on Bleomycin-Induced Lung Injury in Mice

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Abstract

Bleomycin (BLM)-induced lung injury consists of excessive inflammatory cell infiltration and fibrosis. IS-741 has been reported to be an anti-inflammatory drug through an inhibitory action on cell adhesion. In this study we investigated whether IS-741 could inhibit the progression of pulmonary fibrosis through inflammatory cell infiltration. Lung injury was induced in female C57BL/6 mice by intratracheal instillation of BLM. IS-741 was administered daily intraperitoneally. The hydroxyproline content and fluid content in the lung on Day 28 were significantly lower in the IS-741-treated mice. The histological degree of lung injury or fibrosis was reduced in IS-741-treated mice. Administration of IS-741 caused significant reduction in the absolute number of total cells, monocyte chemoattractant protein (MCP)-1, and cysteinyl leukotriene (cysLTs) levels in bronchoalveolar lavage fluid on Day 7. Furthermore, the hydroxyproline content was significantly lower in IS-741-treated mice even though IS-741 was started on Day 14 after BLM instillation. Treatment with IS-741 had an inhibitory effect on BLM-induced lung injury and fibrosis via the repression of MCP-1 or cysLTs in this murine experimental model.

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Acknowledgments

This study was supported by the Health and Labour Sciences Research Grants on Diffuse Lung Diseases from the Japanese Ministry of Health, Labour and Welfare, Grant for Promotion of Niigata University Research Projects (90), and Research Grant from Shimane University Medical School Alumni Association.

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Authors and Affiliations

  1. Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan

    Yuichi Shimaoka, Shunji Tajima, Fumio Fujimori, Cristiane Yamabayashi, Hiroshi Moriyama, Masaki Terada, Toshinori Takada, Eiichi Suzuki & Ichiei Narita

  2. Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan

    Masashi Bando & Yukihiko Sugiyama

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  1. Yuichi Shimaoka
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  2. Shunji Tajima
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  3. Fumio Fujimori
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Correspondence to Shunji Tajima.

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Shimaoka, Y., Tajima, S., Fujimori, F. et al. Effects of IS-741, a Synthetic Anti-Inflammatory Agent, on Bleomycin-Induced Lung Injury in Mice. Lung 187, 331–339 (2009). https://doi.org/10.1007/s00408-009-9162-6

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  • DOI: https://doi.org/10.1007/s00408-009-9162-6

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