title: p53 in fibroblast-like synoviocytes can regulate T helper cell functions in patients with active rheumatoid arthritis.
abstract: BACKGROUND
  p53 is a tumor suppressor and plays a key role in regulating cell hyperplasia, repairing DNA and inducing apoptosis. This study was to investigate p53 expression in fibroblast-like synoviocytes (FLS) and its effect on CD4(+) T lymphocytes from patients with active rheumatoid arthritis (RA).
  
  
  METHODS
  Human FLS were transfected with p53 siRNA and cocultured with CD4(+) T lymphocytes from patients with active RA. The expressions of osteoprotegerin and interleukin (IL)-6 were detected in p53 siRNA and scramble siRNA-transfected FLS. In addition, protein levels of interferon (IFN)-γ, IL-17, IL-4 and CD25 as well as mRNAs of IFN-γ, retinoic acid-related orphan receptor (ROR)-γt, IL-17 and Foxp3 in cocultured CD4(+) T lymphocytes were also measured.
  
  
  RESULTS
  IL-6 decreased in p53-knockdown FLS while osteoprotegerin expression was not altered. FLS with p53 deletion significantly increased the production of IL-17 and IFN-γ by CD4(+) T cells and upregulated Foxp3 mRNA expression without effects on the proportion of CD4(+)CD25(high) T lymphocytes.
  
  
  CONCLUSIONS
  p53 in FLS might regulate Th1 and Th17 functions in patients with RA and participate in the pathogenesis of RA.
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100032, China.
authors.forename: Bi-Xia
authors.initials: BX
authors.lastname: Tang
authors.forename: Xin
authors.initials: X
authors.lastname: You
authors.forename: Li-Dan
authors.initials: LD
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Fu-Lin
authors.initials: FL
authors.lastname: Tang
authors.forename: De-Nian
authors.initials: DN
authors.lastname: Ba
authors.forename: Wei
authors.initials: W
authors.lastname: He
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015850:Interleukin-6; D016159:Tumor Suppressor Protein p53