Effect of Itraconazoles on the Production of Pro-inflammatory Substances in Mouse Macrophage-like Cells

被引：1

作者：

Kato, Takao ^{[2
]}

Horie, Norio ^{[2
,3
]}

Hashimoto, Ken ^{[1
]}

Satoh, Kazue ^{[1
,5
]}

Shimoyama, Tetsuo ^{[2
]}

Kaneko, Tadayoshi ^{[3
,4
]}

Kusama, Kaoru ^{[3
]}

Sakagami, Hiroshi ^{[1
]}

机构：

[1] Meikai Univ, Sch Dent, Dept Diagnost & Therapeut Sci, Div Pharmacol, Saitama 3500283, Japan

[2] Saitama Med Univ, Dept Oral Surg, Saitama Med Ctr, Saitama 3508550, Japan

[3] Meikai Univ, Sch Dent, Div Pathol, Saitama 3500283, Japan

[4] Tokyo Med Univ, Dept Oral & Maxillofacial Surg, Shinjyuku Ku, Tokyo 1600023, Japan

[5] Showa Univ, Sch Med, Dept Anat, Shinagawa Ku, Tokyo 1428555, Japan

来源：

IN VIVO | 2010年 / 24卷 / 05期

关键词：

Hydroxyitraconazole; itraconazole; macrophage; NO; PGE(2); IL-1; beta; TNF-alpha; pro-inflammatory substances; HYDROXY-ITRACONAZOLE; ANTIFUNGAL ACTIVITY; NITRIC-OXIDE; IN-VITRO;

D O I：

暂无

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background, Materials and Methods: Synthetic triazoles are widely used for the treatment of fun gal infection. In order to understand their possible anti-inflammatory action, we investigated the effect of itraconazole and its hydroxylated derivative (hydroxyitraconazole) on the production of various pro-inflammatory substances by mouse macrophage-like RAW264.7 cells. Results: These compounds did not apparently show any growth inhibitory or stimulatory effects over a wide range of concentrations (0.2-50 mu g/ml). Itraconazoles dose-dependently increased the production of prostaglandin E-2 (PGE(2)) and tumor necrosis factor-alpha (TNF-alpha) without affecting the production of interleukin-1 beta (IL-1 beta) and nitric oxide (NO). LPS treatment significantly enhanced the production of NO, PGE(2), TNF-alpha and IL-1 beta. The addition of itraconazoles to LPS-stimulated RAW264.7 cells significantly reduced the production of NO, but rather enhanced the production of PGE(2),TNF-alpha and IL-1 beta. ESR spectroscopy demonstrated that itraconazoles did not significantly scavenge NO and superoxide anion radicals, indicating that the inhibition of NO production by itraconazoles is not due to their radical-scavenging activity. Hydroxyitraconazole was slightly more cytostatic, and more efficiently inhibited NO production, but enhanced the production of other pro-inflammatory substances. Conclusion: These data suggest that itraconazoles regulate NO and other pro-inflammatory substances differently in activated macrophages.

引用

页码：709 / 713

页数：5

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