Tranilast, an orally active anti-allergic drug, up-regulates the anti-inflammatory heme oxygenase-1 expression but down-regulates the pro-inflammatory cyclooxygenase-2 and inducible nitric oxide synth
- 作者：Hyun-Ock Pae ; Sun-Oh Jeong ; Bon Soon Koo ; Hun-Yong Ha ; Kang-Min Lee ; Hun-Taeg Chung
- 关键词：Tranilast ; Heme oxygenase-1 ; Extracellular signal-regulated kinase-1/2 ; Cyclooxygenase-2 ; Inducible nitric oxide synthase ; Tumor necrosis factor-
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- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2008
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：4 July 2008
- 卷：371
- 期：3
- 页码：361-365
- 文件大小：355 K
摘要
Tranilast (N-[3′,4′-dimethoxycinnamonyl] anthranilic acid), an orally active anti-allergic drug, is reported to exert the anti-inflammatory effects, but the underlying mechanisms that could explain the anti-inflammatory actions of tranilast remain largely unknown. Here, we found that tranilast induces heme oxygenase-1 (HO-1) expression through the extracellular signal-regulated kinase-1/2 (ERK1/2) pathway in RAW264.7 macrophages. Tranilast suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide (NO) synthase (iNOS) expression, and thereby reduced COX-2-derived prostaglandin E2 (PGE2) and iNOS-derived NO production in lipopolysaccharide (LPS)-stimulated macrophages. Similarly, tranilast diminished tumor necrosis factor-
(TNF-) and interleukin-1β (IL-1β) production. Interestingly, the effects of tranilast on LPS-induced PGE2, NO, TNF-, and IL-1β production were partially reversed by the HO-1 inhibitor tin protoporphyrin, suggesting that tranilast-induced HO-1 expression is at least partly responsible for the resulting anti-inflammatory effects of the drug. Thus, HO-1 expression via ERK1/2 activation may be at least one of the possible mechanisms explaining the anti-inflammatory actions of tranilast.
(TNF-) and interleukin-1β (IL-1β) production. Interestingly, the effects of tranilast on LPS-induced PGE2, NO, TNF-, and IL-1β production were partially reversed by the HO-1 inhibitor tin protoporphyrin, suggesting that tranilast-induced HO-1 expression is at least partly responsible for the resulting anti-inflammatory effects of the drug. Thus, HO-1 expression via ERK1/2 activation may be at least one of the possible mechanisms explaining the anti-inflammatory actions of tranilast.