6,7-DIMETHOXY-4-METHYLCOUMARIN SUPPRESSES PRO-INFLAMMATORY MEDIATOR EXPRESSION THROUGH INACTIVATION OF THE NF-kappa B AND MAPK PATHWAYS IN LPS-INDUCED RAW 264.7 CELLS
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Title
- 6,7-DIMETHOXY-4-METHYLCOUMARIN SUPPRESSES PRO-INFLAMMATORY MEDIATOR EXPRESSION THROUGH INACTIVATION OF THE NF-kappa B AND MAPK PATHWAYS IN LPS-INDUCED RAW 264.7 CELLS
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Author(s)
- Kim, K.-N.; Yang, H.-W.; Ko, S.-C.; Ko, Y.-J.; Kim, E.-A.; Roh, S.W.; Ko, E.-Y.; Ahn, G.; Heo, S.-J.; Jeon, Y.-J.; Yoon, W.-J.; Hyun, C.-G.; Kim, D.
- KIOST Author(s)
- Heo, Soo Jin(허수진)
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Alternative Author(s)
- 허수진
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Publication Year
- 2014
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Abstract
- In this study, we investigated the ability of 6,7-dimethoxy-4-methylcoumarin (DMC) to inhibit lipopolysaccharide (LPS)-induced expression of pro-inflammatory mediators in mouse macrophage (RAW 264.7) cells, and the molecular mechanism through which this inhibition occurred. Our results indicated that DMC downregulated LPS-induced nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, thereby reducing the production of NO and prostaglandin E2 (PGE2) in LPS-activated RAW 264.7 cells. Furthermore, DMC suppressed LPS-induced production ofpro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. To elucidate the mechanism underlying the antiinflammatory activity of DMC, we assessed itseffects on the mitogen-activated protein kinase (MAPK) pathway and the activity and expression of nuclear transcription factor kappa-B (NF-κB). The experiments demonstrated that DMC inhibited LPS-induced phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (JNK), and p38. In addition, it attenuated LPS-induced NF-κB activation via the inhibition of IκB-α phosphorylation. Taken together, these data suggest that DMC exerts its anti-inflammatory effects in RAW 264.7 cells through the inhibition of LPS-stimulated NF-κB and MAPK signaling, thereby downregulating the expression of pro-inflammatory mediators.
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ISSN
- 1611-2156
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URI
- https://sciwatch.kiost.ac.kr/handle/2020.kiost/2926
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Bibliographic Citation
- EXCLI Journal, v.13, pp.792 - 800, 2014
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Publisher
- Leibniz Research Centre for Working Environment and Human Factors
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Keywords
- 6,7-Dimethoxy-4-methylcoumarin (DMC); Anti-inflammatory; MAPKs; NF-κB; RAW 264.7 cells
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Type
- Article
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Language
- English
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Document Type
- Article
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