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T. Koto, Y. Oike, N. Nagai, S. Satofuka, T. Kurihara, H. Mochimaru, Y. Ozawa, M. Inoue, K. Tsubota, S. Ishida; Suppression of Endotoxin–Induced Uveitis by Calcium–Channel Blockers . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2578.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the anti–inflammatory effects of nifedipine and nilvadipine, calcium–channel blockers, on ocular inflammation in endotoxin–induced uveitis (EIU).
EIU was induced in C57BL/6 mice by a single intraperitoneal injection of 150 µg lipopolysaccharide (LPS) from Escherichia coli in 150 µl phosphate–buffered saline solution. Nifedipine or nilvadipine was injected intraperitoneanlly daily from 5 days before the injection of LPS. Twenty–four hours after administration of LPS, leukocyte adhesion was evaluated with a concanavalin A lectin perfusion–labeling technique. Retinal mRNA and protein levels of intercellular adhesion molecule–1 (ICAM–1) and monocyte chemotactic protein–1 (MCP–1) were examined by RT–PCR and ELISA, respectively.
EIU mice showed significant increases in leukocyte adhesion and in retinal ICAM–1 and MCP–1 mRNA and protein levels. The number of adherent leukocytes was significantly decreased in nifedipine–treated (114.2 ± 28.9 cells, P < 0.01) and nilvadipine–treated (161.0 ± 45.8 cells, P<0.05) EIU mice compared to vehicle–treated EIU mice (217.7 ± 67.7 cells). The retinal ICAM–1 and MCP–1 mRNA levels were decreased in nifedipine–treated and nilvadipine–treated EIU mice compared to controls. Retinal ICAM–1 protein levels were significantly (P < 0.05) lower in nilvadipine–treated EIU mice than in vehicle–treated EIU mice, whereas nifedipine–treated EIU mice tended to have reduced protein levels, but the difference was not statistically significant. Retinal MCP–1 protein levels in nifedipine–treated and nilvadipine–treated EIU mice were significantly (P < 0.05) lower than in vehicle–treated EIU mice.
Calcium channel blockers reduce the LPS–induced increases in leukocyte adhesion and in retinal ICAM–1 and MCP–1 mRNA and protein levels in the murine EIU model. These results suggest the anti–inflammatory effects of nifedipine and nilvadipine and their potential use as a therapeutic agent to reduce ocular inflammation.
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