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

Biochemical and Biophysical Research Communications
Hyun-Ock PaeHun-Taeg Chung

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 E(2) (PGE(2)) and iNOS-derived NO production in lipopolysaccharide (LPS)-stimulated macrophages. Similarly, tranilast diminished tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) production. Interestingly, the effects of tranilast on LPS-induced PGE(2), NO, TNF-alpha, and IL-1beta 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 tran...Continue Reading

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Citations

Jun 22, 2013·Cardiovascular Research·Yuko IwataShigeo Wakabayashi
Apr 23, 2014·PloS One·Tien Van PhanHye-Seon Choi
Sep 10, 2014·Journal of the Neurological Sciences·Mitsuru HanadaYukihiro Matsuyama
Jan 20, 2016·Canadian Journal of Physiology and Pharmacology·Eman SaidRania R Abdelaziz
Jan 29, 2011·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Mee-Young LeeHyeun-Kyoo Shin
Apr 2, 2014·Medical Hypotheses·Amir Hossein NorooznezhadKimia Ahmadi
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Aug 9, 2020·Allergologia et immunopathologia·M EslamiB Yousefi
Feb 24, 2021·BMC Complementary Medicine and Therapies·Xiaoxiao ZhangNing Gu
Mar 1, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Shukur Wasman SmailMuhammad Safdar
Jul 9, 2020·Heliyon·Rikard LandbergLena H Dimberg
Sep 9, 2021·Journal of Experimental Orthopaedics·Junpei DanMasahiko Ikeuchi

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