title: Paeonol inhibited TNFα-induced GM-CSF expression in fibroblast-like synoviocytes.
abstract: OBJECTIVE
  Granulocyte macrophage colony-stimulating factor (GM-CSF) has been proved to be among the most important chemokines, playing a key role in rheumatoid arthritis (RA). However, the mechanism underlying the regulation of GM-CSF has not been established clearly yet. The aim of this study was to investigate the influence of paeonol in the expression of GM-CSF in fibroblast-like synoviocytes (FLS).
  
  
  METHODS
  The expression of GM-CSF was detected both at protein and mRNA levels in FLS after the stimulation of TNF-α at diverse concentrations and times. And then GM-CSF was detected again after pre-treatment with paeonol. Phosphorylation of PI3K/Akt and expression of NF-κB and p-I-κB-αwere detected with western blot. Meanwhile, inhibitors of the pathways were used to investigate the mechanism of regulation of GM-CSF.
  
  
  RESULTS
  Recombinant TNF-α up-regulated GM-CSF in a concentration- and time-dependent manner in FLS, which was significantly suppressed by paeonol. Paeonol also exerted its ability to suppress the promoting effects of TNF-α on the phosphorylation of PI3K/Akt and activation of NF-κB pathway. Administration of the inhibitors LY294002, perifosine, BAY11-7082, and SC-514 confirmed the roles of PI3K/Akt and NF-κB on the production of GM-CSF. Furthermore, TNF-α induced proliferation, while paeonol suppressed proliferation of FLS.
  
  
  CONCLUSIONS
  These results demonstrate that paeonol suppressed TNF-α-induced GM-CSF production via the PI3K/Akt/NF-κB pathway.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Pin
authors.initials: P
authors.lastname: Li
authors.forename: Shu-huan
authors.initials: SH
authors.lastname: Lin
authors.forename: Yi-qing
authors.initials: YQ
authors.lastname: Zheng
authors.forename: Xiang-xiong
authors.initials: XX
authors.lastname: Zheng
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D016328:NF-kappa B / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D013583:Synovial Membrane / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000098:Acetophenones; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C013638:paeonol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt