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 synthase expression in RAW264.7 macrophages |
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Authors: | Pae Hyun-Ock Jeong Sun-Oh Koo Bon Soon Ha Hun-Yong Lee Kang-Min Chung Hun-Taeg |
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Institution: | a Department of Microbiology and Immunology, Wonkwang University School of Medicine, Shinyong-Dong, 344-2, Iksan, Chonbuk 570-749, Republic of Korea b Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Chonbuk 570-749, Republic of Korea c Division of Biological Sciences, College of Natural Science, Chonbuk National University, Jeonju, Chonbuk 561-756, Republic of Korea |
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Abstract: | 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-α (TNF-α) and interleukin-1β (IL-1β) production. Interestingly, the effects of tranilast on LPS-induced PGE2, NO, TNF-α, 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. |
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Keywords: | Tranilast Heme oxygenase-1 Extracellular signal-regulated kinase-1/2 Cyclooxygenase-2 Inducible nitric oxide synthase Tumor necrosis factor-α Interleukin-1β Macrophage Inflammation |
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