JS-III-49, a hydroquinone derivative, exerts anti-inflammatory activity by targeting Akt and p38
The Korean Journal of Physiology and Pharmacology
; : 345-352, 2017.
Article
in En
| WPRIM
| ID: wpr-727982
Responsible library:
WPRO
ABSTRACT
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 macrophage-mediated inflammatory responses. JS-III-49 suppressed the production of the inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2) and down-regulated 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-1b without cytotoxicity in LPS-stimulated RAW264.7 cells. JS-III-49 inhibited nuclear translocation of the NF-kB transcription factors p65 and p50 by directly targeting Akt, an upstream kinase of the NF-kB 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 LPS-stimulated RAW264.7 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-kB and AP-1 pathways, respectively.
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Full text:
1
Index:
WPRIM
Main subject:
Phosphotransferases
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Protein Kinases
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Transcription Factors
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RNA, Messenger
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Dinoprostone
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Cytokines
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NF-kappa B
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Interleukin-6
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Transcription Factor AP-1
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Cyclooxygenase 2
Language:
En
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2017
Type:
Article