p53 in fibroblast-like synoviocytes can regulate T helper cell functions in patients with active rheumatoid arthritis.
- Author:
Bi-Xia TANG
1
;
Xin YOU
;
Li-Dan ZHAO
;
Yang LI
;
Xuan ZHANG
;
Fu-Lin TANG
;
De-Nian BA
;
Wei HE
Author Information
- Publication Type:Journal Article
- MeSH: Arthritis, Rheumatoid; genetics; immunology; metabolism; CD4-Positive T-Lymphocytes; metabolism; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Forkhead Transcription Factors; genetics; metabolism; Humans; Interleukin-6; genetics; metabolism; Reverse Transcriptase Polymerase Chain Reaction; Synovial Membrane; cytology; Tumor Suppressor Protein p53; genetics; metabolism
- From: Chinese Medical Journal 2011;124(3):364-368
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDp53 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).
METHODSHuman 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.
RESULTSIL-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.
CONCLUSIONp53 in FLS might regulate Th1 and Th17 functions in patients with RA and participate in the pathogenesis of RA.
