成纤维样滑膜细胞中的 p53 可调节活动期类风湿关节炎患者的辅助性 T 细胞功能。

p53 in fibroblast-like synoviocytes can regulate T helper cell functions in patients with active rheumatoid arthritis.

机构信息

Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100032, China.

出版信息

Chin Med J (Engl). 2011 Feb;124(3):364-8.

PMID:21362334

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.

CONCLUSION

p53 in FLS might regulate Th1 and Th17 functions in patients with RA and participate in the pathogenesis of RA.

摘要

背景

p53 是一种肿瘤抑制因子，在调节细胞过度增生、修复 DNA 和诱导细胞凋亡方面发挥着关键作用。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 CD4+T 淋巴细胞的影响。

方法

采用 p53 siRNA 转染人 FLS，并与 RA 活动期患者的 CD4+T 淋巴细胞共培养。检测 p53 siRNA 和 scramble siRNA 转染的 FLS 中骨保护素和白细胞介素（IL）-6 的表达。此外，还检测了共培养的 CD4+T 淋巴细胞中干扰素（IFN）-γ、IL-17、IL-4 和 CD25 的蛋白水平以及 IFN-γ、维甲酸相关孤儿受体（ROR）-γt、IL-17 和 Foxp3 的 mRNA 水平。