title: Protective effect of allograft inflammatory factor-1 on the apoptosis of fibroblast-like synoviocytes in patients with rheumatic arthritis induced by nitro oxide donor sodium nitroprusside.
abstract: OBJECTIVE
  Inadequate apoptosis of rheumatic arthritis (RA) fibroblast-like synoviocytes (FLS) plays a crucial role in the immunopathogenesis of RA. Allograft inflammatory factor-1 (AIF-1) is a novel member of the cytokine network that has been found to be involved in the immunological process underlying RA. This study was undertaken to investigate the potential effects of AIF-1 on nitric oxide donor (NO) sodium nitroprusside (SNP)-induced RA-FLS apoptosis, and the possible molecular mechanisms underlying these effects.
  
  
  METHODS
  FLS obtained from patients with active RA were cultured in vitro and treated with SNP in the present or absence of AIF-1. RA-FLS viability was tested by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. RA-FLS apoptosis was analysed by flow cytometry and terminal dUTP nick-end labeling (TUNEL). The levels of phospho-Akt (p-Akt) and phospho-BAD (p-BAD) protein were detected by Western blot.
  
  
  RESULTS
  A 24-h AIF-1 pretreatment at concentrations ranging from 10 to 100 ng/mL increased the viability of RA-FLS and prevented RA-FLS apoptosis in a dose-dependent manner in the presence of SNP. AIF-1 induced phosphorylation of Akt and BAD in a time- and concentration-dependent manner. The effect was reversed by treatment with the PI3K inhibitor LY2940042 (LY) and the nuclear factor kappa B (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC).
  
  
  CONCLUSIONS
  AIF-1 can protect RA-FLS from apoptosis induced by NO by upregulating the expression of p-Akt and p-BAD.
authors.affiliation: Department of Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Mei
authors.forename: R
authors.initials: R
authors.lastname: Du
authors.forename: L
authors.initials: L
authors.lastname: Shen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002135:Calcium-Binding Proteins; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006304:Health Status; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010766:Phosphorylation; D011759:Pyrrolidines / Q000494:pharmacology; D012213:Rheumatic Fever / Q000473:pathology* / Q000503:physiopathology; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology*; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D002867:Chromones; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D008840:Microfilament Proteins; D009025:Morpholines; D020030:Nitric Oxide Donors; D011759:Pyrrolidines; D013859:Thiocarbamates; D009599:Nitroprusside; C020972:pyrrolidine dithiocarbamic acid; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one