Effects of IS-741, a synthetic anti-inflammatory agent, on bleomycin-induced lung injury in mice.
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.
Shimaoka
Yuichi
Y
Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.
Tajima
Shunji
S
Fujimori
Fumio
F
Yamabayashi
Cristiane
C
Moriyama
Hiroshi
H
Terada
Masaki
M
Takada
Toshinori
T
Suzuki
Eiichi
E
Bando
Masashi
M
Sugiyama
Yukihiko
Y
Narita
Ichiei
I
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
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