title: Effects of IS-741, a synthetic anti-inflammatory agent, on bleomycin-induced lung injury in mice.
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.
authors: Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.
authors: Yuichi
authors: Y
authors: Shimaoka
authors: Shunji
authors: S
authors: Tajima
authors: Fumio
authors: F
authors: Fujimori
authors: Cristiane
authors: C
authors: Yamabayashi
authors: Hiroshi
authors: H
authors: Moriyama
authors: Masaki
authors: M
authors: Terada
authors: Toshinori
authors: T
authors: Takada
authors: Eiichi
authors: E
authors: Suzuki
authors: Masashi
authors: M
authors: Bando
authors: Yukihiko
authors: Y
authors: Sugiyama
authors: Ichiei
authors: I
authors: Narita
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D018932:Chemokine CCL2 / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007274:Injections, Intraperitoneal; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D011654:Pulmonary Edema / Q000139:chemically induced / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D015289:Leukotrienes; D016169:Lymphocyte Function-Associated Antigen-1; D011725:Pyridines; C112381:cysteinyl-leukotriene; C097462:IS 741; D001761:Bleomycin; D054513:Group IV Phospholipases A2; D003545:Cysteine; D006909:Hydroxyproline