KMID : 0606920150230010039
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Biomolecules & Therapeutics 2015 Volume.23 No. 1 p.39 ~ p.44
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Tolfenamic Acid Suppresses Inflammatory Stimuli-Mediated Activation of NF-¥êB Signaling
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Shao Hong-Jun
Lou Zhiyuan Jeong Jin-Boo Kim Kui-Jin Lee Ji-Hye Lee Seong-Ho
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Abstract
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Tolfenamic acid (TA) is a traditional non-steroid anti-inflammatory drug (NSAID) and has been broadly used for the treatment of migraines. Nuclear factor kappa B (NF-¥êB) is a sequence-specific transcription factor and plays a key role in the development and progression of inflammation and cancer. We performed the current study to investigate the underlying mechanisms by which TA suppresses inflammation focusing on NF-¥êB pathway in TNF-¥á stimulated human normal and cancer cell lines and lipopolysaccharide (LPS)-stimulated mouse macrophages. Different types of human cells (HCT116, HT-29 and HEK293) and mouse macrophages (RAW264.7) were pre-treated with different concentrations of TA and then exposed to inflammatory stimuli such as TNF-¥á and LPS. Transcriptional activity of NF-¥êB, I¥êB-¥á-degradation, p65 translocation and mitogen-activated protein kinase (MAPK) activations were measured using luciferase assay and Western blots. Pre-treatment of TA repressed TNF-¥á- or LPS-stimulated NF-¥êB transactivation in a dose-dependent manner. TA treatment reduced degradation of I¥êB-¥á and subsequent translocation of p65 into nucleus. TA significantly down-regulated the phosphorylation of c-Jun N-terminal kinase (JNK). However, TA had no effect on NF-¥êB signaling and JNK phosphorylation in HT-29 human colorectal cancer cells. TA possesses anti-inflammatory activities through suppression of JNK/NF-¥êB pathway in different types of cells.
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KEYWORD
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Tolfenamic acid, NF-kappa B, Inflammation
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