High CXCR3 expression in synovial mast cells associated with CXCL9 and CXCL10 expression in inflammatory synovial tissues of patients with rheumatoid arthritis.
High CXCR3 expression in synovial mast cells associated with CXCL9 and CXCL10 expression in inflammatory synovial tissues of patients with rheumatoid arthritis.
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DOI：
10.1186/ar783
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发表时间：
2003
影响因子：
4.9
通讯作者：
Stiehl P
中科院分区：
文献类型：
--
作者：
Ruschpler P;Lorenz P;Eichler W;Koczan D;Hänel C;Scholz R;Melzer C;Thiesen HJ;Stiehl P
为了提高我们对类风湿关节炎(RA)病理生理学的认识，我们研究了类风湿关节炎(RA)和骨关节炎(OA)患者滑膜组织中的基因表达模式。应用DNA寡核苷酸芯片技术从RA(n=20)和OA(n=10)的病理分类组织标本中筛选滑膜组织中差异表达的基因。在芯片上显示的7131个基因中，有101个基因在RA中上调，300个基因在RA中下调。采用半定量逆转录聚合酶链式反应、Western blotting和免疫组织化学方法验证基因芯片的表达水平。结果表明，RA患者Cys-X-Cys受体(CXCR1)、CXCR2和CXCR3mRNAs以及Cys-X-Cys配体(CXCL9)(干扰素-γ诱导的单核细胞因子)和CXCL10(干扰素-γ诱导蛋白10)mRNAs均显著上调。Western blotting检测RA滑膜组织中CXCR1和CXCR3的蛋白水平升高。免疫组织化学结果显示，CXCR3蛋白在RA患者滑膜组织中的肥大细胞上优先表达。这些结果表明，RA患者滑膜组织肥大细胞上CXCR3蛋白的大量表达在RA的病理生理过程中起重要作用，并伴随着趋化因子CXCL9和CXCL10水平的升高。成熟的肥大细胞可能促进和维持关节炎病变的炎症状态(例如，通过产生组胺、蛋白酶、花生四烯酸代谢产物和细胞因子等炎症介质)。因此，肥大细胞可能成为治疗干预的潜在靶点。
To improve our knowledge on the pathophysiology of rheumatoid arthritis (RA), we investigated gene expression patterns in synovial tissue from RA and osteoarthritis (OA) patients. DNA oligonucleotide microarray analysis was employed to identify differentially expressed genes in synovial tissue from pathologically classified tissue samples from RA (n = 20) and OA patients (n = 10). From 7131 gene sets displayed on the microarray chip, 101 genes were found to be upregulated and 300 genes to be downregulated in RA as compared with OA. Semiquantitative reverse-transcription polymerase chain reaction, Western blotting and immunohistochemistry were used to validate microarray expression levels. These experiments revealed that Cys–X–Cys receptor (CXCR)1, CXCR2 and CXCR3 mRNAs, as well as Cys–X–Cys ligand (CXCL)9 (monokine induced by IFN-γ) and CXCL10 (IFN-γ inducible protein 10) mRNAs, were significantly upregulated in RA as compared with OA disease. Elevated protein levels in RA synovial tissue were detected for CXCR1 and CXCR3 by Western blotting. Using immunohistochemistry, CXCR3 protein was found to be preferentially expressed on mast cells within synovial tissue from RA patients. These findings suggest that substantial expression of CXCR3 protein on mast cells within synovial tissue from RA patients plays a significant role in the pathophysiology of RA, accompanied by elevated levels of the chemokines CXCL9 and CXCL10. Mature mast cells are likely to contribute to and sustain the inflamed state in arthritic lesions (e.g. by production of inflammatory mediators such as histamine, proteinases, arachidonic acid metabolites and cytokines). Thus, the mast cell could become a potential target in therapeutic intervention.