Sex steroid receptors in rheumatoid arthritis
Sex steroid receptors in rheumatoid arthritis
复制标题
DOI：
10.1042/cs20030317
复制
发表时间：
2004-03-01
期刊：
影响因子：
6
通讯作者：
Sasano, H
中科院分区：
文献类型：
--
作者：
Ishizuka, M;Hatori, M;Sasano, H
类风湿关节炎(RA)是一种以慢性炎性滑膜炎为主要特征的疾病，众所周知，其患病率和临床特征与性别差异显著相关。性激素已被认为与类风湿关节炎的发病机制有关，但有关类固醇受体在类风湿关节炎滑膜组织中表达的细节尚不完全清楚。本研究采用实时定量逆转录聚合酶链式反应(RT-PCR)检测8例女性RA滑膜组织和6例女性非炎症滑膜组织中雌激素受体(ER)α、ER、孕激素受体(PR)和雄激素受体(AIR)的表达，并用免疫组织化学方法检测22例RA患者滑膜组织中ERα、ERβ、PR-A、PR-B和AIR的免疫定位。实时荧光定量RT-PCR检测结果显示，ER、PR和AR在RA和非炎症滑膜组织中均有表达。RA滑膜组织中ER mRNAs的相对丰度显著高于非炎症滑膜组织(P<；0.05)。此外，类风湿关节炎滑膜组织中ERpha/ERbeta的相对表达水平显著低于非炎症滑膜组织(2.34+/-1.60；非炎症滑膜组织，20.7+/-19.1；P<；0.05)。PR基因的相对丰度差异无统计学意义。RA患者AR基因相对丰度显著低于对照组(P<；0.05)。所有患者的衬里细胞、炎性细胞和成纤维细胞均检测到Era、ER、PR-13和AIR免疫反应阳性。ERβ和PR-B在衬里细胞(ERbeta54.2+/-12.2%；PR-13，73.6+/-18.9%)和炎性细胞(ERbeta74.6+/-16.2%；PR-B，75.9+/-16.1%)中的标记指数均高于成纤维细胞(ERbeta，36.5+/-15.6%；PR-13，49.4+/-18.0%)。ERα和AR在衬里细胞(ERα，14.4+/-8.6%；AR，31.2+/-11.3%)和成纤维细胞(ERα，12.1+/-7.5%；AR，20.1+/-9.6%)中的标记指数显著高于炎性细胞(ERα，5.7+/-3.3%；AR，9.2+/-4.4%)。50岁以下RA滑膜成纤维细胞ERα、ERβ和PR-B的标记指数在男女间差异有统计学意义(P<；0.05)。这些结果表明，类固醇受体存在于类风湿关节炎和非炎性滑膜组织中，包括类风湿关节炎的炎性细胞，提示类固醇可能在类风湿关节炎滑膜组织炎症的调节中发挥重要作用。
Rheumatoid arthritis (RA) is a disease characterized primarily by chronic inflammatory synovitis and is well-known to be associated with significant sex differences in its prevalence and clinical features. Sex steroids have been proposed to be involved in the pathogenesis of RA, but details pertaining to the expression of sex steroid receptors in RA synovial tissue have yet to be fully characterized. In the present study, we examined oestrogen receptor (ER) a, ER, progesterone receptor (PR) and androgen receptor (AIR) mRNA expression using real-time reverse transcriptase-PCR (RT-PCR) in eight female RA synovial tissues and six female synovial tissues without inflammation, and determined immunolocalization of ERalpha, ERbeta, PR-A, PR-B and AIR using immunohistochemistry in synovial tissues obtained from 22 RA patients. Real-time RTPCR analysis demonstrated the expression of ER, PR and AR mRNAs in both RA and non-inflamed synovial tissues. Relative abundance of ER mRNAs was significantly higher in RA synovial tissue than non-inflamed synovial tissue (P < 0.05). In addition, the relative ERalpha/ERbeta mRNA expression ratio was significantly lower in RA than non-inflamed synovial tissue (RA, 2.34 +/- 1.60; and non-inflamed, 20.7 +/- 19. 1; P < 0.05). There were no significant differences in relative abundance of PR mRNA. Relative abundance of AR mRNA was significantly lower in RA (P < 0.05). Immunoreactivity for ERa, ER, PR-13 and AIR was detected in the lining cells, inflammatory cells and fibroblasts in all the patients examined. The labelling indices for ERbeta and PR-B were more abundant in both lining cells (ERbeta 54.2 +/- 12.2 %; PR-13, 73.6 +/- 18.9 %) and inflammatory cells (ERbeta 74.6 +/- 16.2 %; PR-B, 75.9 +/- 16.1 %) than in fibroblasts (ERbeta, 36.5 +/- 15.6 %; PR-13, 49.4 +/- 18.0 %). Labelling indices for ERalpha and AR were significantly higher in lining cells (ERalpha, 14.4 +/- 8.6 %; AR, 31.2 +/- 11.3 %) and fibroblasts (ERalpha, 12.1 +/- 7.5 %; AR, 20.1 +/- 9.6 %) than those in inflammatory cells (ERalpha, 5.7 +/- 3.3 %; AR, 9.2 +/- 4.4 %). There were significant differences (P < 0.05) in the labelling indices for ERalpha, ERbeta and PR-B between men and women under 50 years of age in fibroblasts of RA synovial tissues. These results indicate that sex steroid receptors are present in RA and non-inflamed synovial tissues, including inflammatory cells in RA, and suggest that sex steroids may play important roles in the regulation of inflammation of RA synovial tissue.