title: EF24 suppresses maturation and inflammatory response in dendritic cells.
abstract: Synthetic curcuminoid EF24 was studied for its effect on the maturation and inflammatory response in murine bone marrow derived immortalized JAWS II dendritic cells (DCs). EF24 reduced the expression of LPS-induced MHC class II, CD80 and CD86 molecules. It also abrogated the appearance of dendrites, a typical characteristic of mature DCs. These effects were accompanied by the inhibition of LPS-induced activation of transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB). Simultaneous reduction of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, IL-6] both at the mRNA and secreted levels was also observed. To investigate the dependency of LPS effects on MyD88 adaptor protein, we transfected JAWS II DCs with dominant negative MyD88 plasmid construct (MyD88-DN). EF24 reduced NF-κB activity and TNF-α secretion in a MyD88-dependent manner. These results suggest that EF24 modulates DCs by suppressing their maturation and reducing the secretion of inflammatory cytokines. Further, it appears that EF24 acts at or upstream of MyD88 in the LPS-TLR4/MyD88/NF-κB pathway.
authors.affiliation: Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, Oklahoma City, 73117, USA.
authors.forename: Prachi
authors.initials: P
authors.lastname: Vilekar
authors.forename: Shanjana
authors.initials: S
authors.lastname: Awasthi
authors.forename: Aravindan
authors.initials: A
authors.lastname: Natarajan
authors.forename: Shrikant
authors.initials: S
authors.lastname: Anant
authors.forename: Vibhudutta
authors.initials: V
authors.lastname: Awasthi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003474:Curcumin / Q000031:analogs & derivatives; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010881:Piperidones / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: C524042:3,5-bis(2-fluorobenzylidene)piperidin-4-one; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001597:Benzylidene Compounds; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010881:Piperidones; D003474:Curcumin