title: Salvianolic acid B suppresses maturation of human monocyte-derived dendritic cells by activating PPARγ.
abstract: OBJECTIVE
  Salvianolic acid B (Sal B), a water-soluble antioxidant derived from a Chinese medicinal herb, is known to be effective in the prevention of atherosclerosis. Here, we tested the hypothesis that the anti-atherosclerotic effect of Sal B might be mediated by suppressing maturation of human monocyte-derived dendritic cells (h-monDC).
  
  
  METHODS
  h-monDC were derived by incubating purified human monocytes with GM-CSF and IL-4. h-monDC were pre-incubated with or without Sal B and stimulated by oxidized low-density lipoprotein (ox-LDL) in the presence or absence of PPARγ siRNA. Expression of h-monDC membrane molecules (CD40, CD86, CD1a, HLA-DR) were analysed by FACS, cytokines were measured by elisa and the TLR4-associated signalling pathway was determined by Western blotting.
  
  
  RESULTS
  Ox-LDL promoted h-monDC maturation, stimulated CD40, CD86, CD1a, HLA-DR expression and IL-12, IL-10, TNF-α production; and up-regulated TLR4 signalling. These effects were inhibited by Sal B. Sal B also triggered PPARγ activation and promoted PPARγ nuclear translocation, attenuated ox-LDL-induced up-regulation of TLR4 and myeloid differentiation primary-response protein 88 and inhibited the downstream p38-MAPK signalling cascade. Knocking down PPARγ with the corresponding siRNA blocked these effects of Sal B.
  
  
  CONCLUSIONS
  Our data suggested that Sal B effectively suppressed maturation of h-monDC induced by ox-LDL through PPARγ activation.
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.forename: Hongying
authors.initials: H
authors.lastname: Liu
authors.forename: Shijun
authors.initials: S
authors.lastname: Wang
authors.forename: Dazhuo
authors.initials: D
authors.lastname: Shi
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Keqiang
authors.initials: K
authors.lastname: Wang
authors.forename: Keji
authors.initials: K
authors.lastname: Chen
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D001572:Benzofurans / Q000494:pharmacology*; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D053630:Depsides
chemical_list: D015703:Antigens, CD; D001572:Benzofurans; D016207:Cytokines; D017931:DNA Primers; D008077:Lipoproteins, LDL; D053594:Myeloid Differentiation Factor 88; D047495:PPAR gamma; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4; C507779:MYD88 protein, human; C495345:TLR4 protein, human; C099252:oxidized low density lipoprotein; C076944:salvianolic acid B; D053630:Depsides