JS-III-49, a hydroquinone derivative, exerts anti-inflammatory activity by targeting Akt and p38.
10.4196/kjpp.2017.21.3.345
- Author:
Young Su YI
1
;
Mi Yeon KIM
;
Jae Youl CHO
Author Information
1. Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea. jaecho@skku.edu
- Publication Type:Original Article
- Keywords:
Akt;
Anti-inflammatory activity;
HQ derivative;
JS-III-49;
Macrophages;
p38
- MeSH:
Cyclooxygenase 2;
Cytokines;
Dinoprostone;
Interleukin-6;
Macrophages;
NF-kappa B;
Nitric Oxide;
Nitric Oxide Synthase Type II;
Phosphotransferases;
Protein Kinases;
RNA, Messenger;
Transcription Factor AP-1;
Transcription Factors
- From:The Korean Journal of Physiology and Pharmacology
2017;21(3):345-352
- CountryRepublic of Korea
- Language:English
-
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.
