p53 in fibroblast-like synoviocytes can regulate T helper cell functions in patients with active rheumatoid arthritis
p53 in fibroblast-like synoviocytes can regulate T helper cell functions in patients with active rheumatoid arthritis
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成纤维细胞样滑膜细胞中的 p53 可以调节活动性类风湿关节炎患者的 T 辅助细胞功能。
DOI：
10.3760/cma.j.issn.0366-6999.2011.03.008
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发表时间：
2011-02-05
影响因子：
6.1
通讯作者：
He Wei
中科院分区：
文献类型：
--
作者：
Tang Bi-xia;You Xin;He Wei
背景p53是一种肿瘤抑制因子，在调节细胞增殖、DNA修复和诱导凋亡中起重要作用。本研究旨在探讨类风湿关节炎（RA）患者成纤维样滑膜细胞（FLS）中p53的表达及其对CD 4 + T淋巴细胞的影响。方法将p53 siRNA转染人FLS，与活动期RA患者的CD 4 + T淋巴细胞共培养。检测转染p53 siRNA和scramble siRNA的FLS中骨保护素（osteoprotegerin）和白细胞介素（IL）-6的表达。此外，还测量了共培养的CD 4（+）T淋巴细胞中干扰素（IFN）-γ、IL-17、IL-4和CD 25的蛋白水平以及IFN-γ、视黄酸相关孤儿受体（ROR）-γ t、IL-17和Foxp 3的mRNA。结果p53基因敲低的FLS中IL-6表达降低，而骨保护素表达无明显变化。p53缺失的FLS显著增加了CD 4（+）T细胞产生IL-17和IFN-γ的能力，上调了Foxp 3 mRNA的表达，但对CD 4（+）CD 25（high）T淋巴细胞的比例没有影响。结论FLS中p53可能通过调节RA患者Th 1和Th 17细胞功能参与RA的发病。中华医学杂志2011;124（3）：364-368
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)-gamma gamma, IL-17, IL-4 and CD25 as well as mRNAs of IFN-gamma, retinoic acid-related orphan receptor (ROR)-gamma t, 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-gamma by CD4(+) T cells and upregulated Foxp3 mRNA expression without effects on the proportion of CD4(+)CD25(high) T lymphocytes. Conclusion p53 in FLS might regulate Th1 and Th17 functions in patients with RA and participate in the pathogenesis of RA. Chin Med J2011;124(3):364-368