title: [S632A3 promotes LPS-induced IFN-beta production through inhibiting the activation of GSK-3beta].
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.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Song
authors.forename: Dian-Dong
authors.initials: DD
authors.lastname: Li
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Deng
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D010881:Piperidones / Q000494:pharmacology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D010881:Piperidones; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C511904:S632A3; D016899:Interferon-beta; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3