KMID : 0811720170210030345
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Korean Journal of Physiology & Pharmacology 2017 Volume.21 No. 3 p.345 ~ p.352
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JS-III-49, a hydroquinone derivative, exerts anti-inflammatory activity by targeting Akt and p38
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Yi Young-Su
Kim Mi-Yeon Cho Jae-Youl
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Abstract
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Since previous studies have reported that hydroquinone (HQ) exerted immunosuppressive and anti-inflammatory activity, various HQ derivatives have been synthesized and their biological activities investigated. In this study, we explored the anti-inflammatory activity of JS-III-49, a novel HQ derivative, in macrophagemediated inflammatory responses. JS-III-49 suppressed the production of the inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2) and downregulated the mRNA expression of the inflammatory enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-1¥â without cytotoxicity in LPS-stimulated RAW264.7 cells. JS-III-49 inhibited nuclear translocation of the NF-¥êB transcription factors p65 and p50 by directly targeting Akt, an upstream kinase of theNF-¥êB pathway, in LPS-stimulated RAW264.7 cells. However, JS-III-49 did not directly inhibit the kinase activities of Src and Syk, which are upstream kinases of Akt, in LPSstimulatedRAW264.7 cells. Moreover, JS-III-49 suppressed the nuclear translocation of c-Fos, one of the components of AP-1, by specifically targeting p38, an upstream mitogen-activated protein kinase (MAPK) in the AP-1 pathway in LPS-stimulated RAW264.7 cells. These results suggest that JS-III-49 plays an anti-inflammatory role in LPS-stimulated macrophages by targeting Akt and p38 in the NF-¥êB and AP-1 pathways, respectively.
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KEYWORD
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Akt, Anti-inflammatory activity, HQ derivative, JS-III-49, Macrophages, p38
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