系统性硬化症患者表皮中白细胞介素-21受体的表达

Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis.

作者信息

Distler Jörg H W, Jüngel Astrid, Kowal-Bielecka Otylia, Michel Beat A, Gay Renate E, Sprott Haiko, Matucci-Cerinic Marco, Chilla Meike, Reich Kristian, Kalden Joachim R, Müller-Ladner Ulf, Lorenz Hanns M, Gay Steffen, Distler Oliver

机构信息

University Hospital Zurich, Zurich, Switzerland.

出版信息

Arthritis Rheum. 2005 Mar;52(3):856-64. doi: 10.1002/art.20883.

DOI:10.1002/art.20883

PMID:15751077

Abstract

OBJECTIVE

To examine the expression and regulation of interleukin-21 (IL-21) and IL-21 receptor (IL-21R) in patients with systemic sclerosis (SSc; scleroderma).

METHODS

Skin biopsy specimens were obtained from 23 patients with SSc and 15 healthy controls. IL-21/IL-21R messenger RNA (mRNA) was quantified using real-time polymerase chain reaction (PCR). The expression pattern of IL-21/IL-21R was analyzed by in situ hybridization and Western blotting. Stimulation experiments were performed with cultured dermal fibroblasts from patients with SSc and healthy controls as well as with keratinocytes, using IL-1beta, platelet-derived growth factor BB, monocyte chemoattractant protein 1, transforming growth factor beta, and IL-21. The SCID-hu skin mouse model was used for in vivo experiments.

RESULTS

IL-21R mRNA was detected in all biopsy specimens from patients with SSc and controls, with a 4.7-fold increase observed in SSc samples. In situ hybridization and immunohistochemical analysis showed an up-regulation of IL-21R in samples of epidermis from SSc patients, whereas no signal was detected in skin specimens from healthy controls. These results were confirmed in vitro, in that cultured keratinocytes expressed significant levels of IL-21R, whereas no signal was observed in fibroblasts. Interestingly, mRNA for IL-21 could not be detected by real-time PCR and in situ hybridization. Various concentrations of key cytokines in the pathogenesis of SSc did not stimulate the expression of IL-21R mRNA in cultured keratinocytes and dermal fibroblasts. In the SCID mouse transplantation model, the overexpression of IL-21R mRNA in SSc keratinocytes remained unchanged after transplantation.

CONCLUSION

The up-regulation of IL-21R in keratinocytes indicates that, similar to fibroblasts and endothelial cells, the expression pattern is altered in SSc. Moreover, the expression of IL-21R appears to be independent of key cytokines that are operant in SSc.

摘要

目的

检测白细胞介素-21（IL-21）及其受体（IL-21R）在系统性硬化症（SSc；硬皮病）患者中的表达及调控情况。

方法

获取23例SSc患者及15名健康对照者的皮肤活检标本。采用实时聚合酶链反应（PCR）定量检测IL-21/IL-21R信使核糖核酸（mRNA）。通过原位杂交和蛋白质免疫印迹法分析IL-21/IL-21R的表达模式。使用IL-1β、血小板衍生生长因子BB、单核细胞趋化蛋白1、转化生长因子β和IL-21对SSc患者及健康对照者的培养真皮成纤维细胞以及角质形成细胞进行刺激实验。采用重症联合免疫缺陷（SCID）-人皮肤小鼠模型进行体内实验。

结果

在所有SSc患者及对照者的活检标本中均检测到IL-21R mRNA，SSc样本中其表达量增加了4.7倍。原位杂交和免疫组化分析显示，SSc患者表皮样本中IL-21R表达上调，而健康对照者的皮肤标本中未检测到信号。体外实验证实了这些结果，即培养的角质形成细胞表达高水平的IL-21R，而成纤维细胞中未观察到信号。有趣的是，通过实时PCR和原位杂交未检测到IL-21的mRNA。SSc发病机制中的各种关键细胞因子的不同浓度均未刺激培养的角质形成细胞和真皮成纤维细胞中IL-21R mRNA的表达。在SCID小鼠移植模型中，移植后SSc角质形成细胞中IL-21R mRNA的过表达保持不变。