S632A3 promotes LPS-induced IFN-beta production through inhibiting the activation of GSK-3beta.
- Author:
Na ZHANG
1
;
Xin YANG
;
Rong XU
;
Zhen WANG
;
Dan-Qing SONG
;
Dian-Dong LI
;
Hong-Bin DENG
Author Information
1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Anti-Bacterial Agents;
pharmacology;
Cell Line;
Enzyme Activation;
drug effects;
Glycogen Synthase Kinase 3;
metabolism;
Glycogen Synthase Kinase 3 beta;
Interferon-beta;
biosynthesis;
genetics;
Lipopolysaccharides;
pharmacology;
Macrophages;
cytology;
metabolism;
Mice;
Phosphorylation;
Piperidones;
pharmacology;
Proto-Oncogene Proteins c-jun;
metabolism;
RNA, Messenger;
metabolism;
RNA, Small Interfering;
genetics;
Transfection
- From:
Acta Pharmaceutica Sinica
2013;48(7):1113-1118
- CountryChina
- Language:Chinese
-
Abstract:
LPS stimulation of macrophages production of IFN-beta plays a key role in innate immunity defending the microbial invasion. In this study, the effect of S632A3 promoting LPS-induced IFN-beta production and the underlying mechanism were investigated, mRNA level was measured by real-time PCR, cytokine production was determined by ELISA, GSK-3beta activity was investigated by kinase assay, protein phosphorylation and expression were evaluated by Western blotting. The results revealed that S632A3 significantly augmented IFN-beta production by LPS-stimulated macrophages. S632A3 inhibition of the activation of GSK-3beta, reduced the threonine 239 phosphorylation of transcription factor c-Jun but increased the total level of c-Jun in LPS-stimulated macrophages. Moreover, small interfering RNA-mediated knockdown of c-Jun level abrogated the ability of S632A3 to augment IFN-beta. The study thus demonstrates S632A3 being a new anti-inflammation lead compound and provides a molecular mechanism by which S632A3 promoted LPS-induced IFN-beta production in macrophages through inhibiting the activation of GSK-3beta.
