成纤维滑膜细胞p53基因表达对类风湿关节炎患者CD4^＋T淋巴细胞的调节

The effect of p53 expression in fibroblast-like synoviocytes on CD4^＋ T iymphocytes in patients with rheumatoid arthritis

目的研究人成纤维滑膜细胞（FLS）p53基因表达对类风湿关节炎（RA）患者CD46^＋T淋巴细胞的调节作用。方法采用小分子干扰RNA（siRNA）转染抑制FLS内p53基因表达，并与RA患者外周血CD4^＋T淋巴细胞共同培养。检测转染后FLS中骨保护素（OPG）表达及白细胞介素（IL）-6分泌。并对与之共培养的CD4^＋细胞膜／胞质内蛋白干扰素（IFN）-1、IL-17、IL-4和CD25以及IFN-γ孤儿核受体γt（RORγt）、IL-17、Foxp3RNA水平进行测定。结果p53基因被抑制后，FLS分泌IL-6减少，但OPG表达未受影响。p53基因被抑制的FLS使共培养的CD4＋T淋巴细胞内IL-17及IFN-1蛋白和RNA表达上调，但对CD4＋T淋巴细胞RORγt RNA影响不大。虽可上调F0xp3表达，但CD4＋CD25^high细胞阳性率并无明显变化。结论FLJS内p53表达对RA外周血Th1、Th17有调节作用。

Objective To investigate that p53 expression in fibroblast-like synoviocytes （FLS） and its effects on CD4^＋ T lymphocytes from active rheumatoid arthritis （RA） patients. Methods Human FLS was transfected with p53siRNA and cocuhured with CD46^＋ T lymphocytes from active RA patients. The expression of osteoprotegerin and IL-6 secretion was detected in the transfected FLS. In addition, the expressions of IFNγ IL-17, IL-4 and CD25 as well as mRNA levels of IFN-γ, ROR3＇t, IL-17 and Foxp3 in cocuhured CD4^＋ T lymphocytes were also measured. Results IL-6 secretion decreased in p53-inhibited FLS while osteoprotegerin expression was not altered, p53-inhibited FLS could significantly increase IL-17 and IFN-γ expressions. It also upregulated Foxp3 expression though had no effect on CD4^＋CD25^high T lymphocytes. Conclusion p53 expression in FLS regulates Thl and Thl7 cells of RA patients, and therefore participate in the pathogenesis of RA.