Inhibition of MAP kinase in synovium by treatment with tocilizumab in rheumatoid arthritis
Inhibition of MAP kinase in synovium by treatment with tocilizumab in rheumatoid arthritis
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DOI：
10.1007/s10067-011-1833-z
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发表时间：
2011-11-01
影响因子：
3.4
通讯作者：
Hobo, Kaori
中科院分区：
文献类型：
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作者：
Kanbe, Katsuaki;Chen, Qian;Hobo, Kaori
为了研究托珠单抗治疗类风湿性关节炎 (RA) 滑膜中丝裂原激活蛋白激酶 (MAPK) 的组织学变化，评估了 10 名接受甲氨蝶呤 (MTX) 治疗的 RA 患者的滑膜组织样本（作为对照）和 10 名接受托珠单抗治疗的 RA 患者的滑膜组织样本。使用苏木精和伊红（H&E）染色观察滑膜，并通过免疫组织化学分析肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）、基质金属蛋白酶-3（MMP-3）、CD4（T细胞）、CD20（B细胞）、CD68（巨噬细胞）、血管内皮生长因子（VEGF）、CD29（β-1）的表达。整合素）、磷酸化 p38 MAPK (Tyr180/Tyr182)、磷酸化 p44/42 MAPK [细胞外信号调节激酶 (ERK) 1/ERK2] 和磷酸化 c-Jun N 末端激酶 (JNK)。 H&E染色显示细胞增殖能力存在显着差异；然而，两组之间的滑膜血管丰富度没有变化。免疫组织化学检查显示，托珠单抗组 CD29（β-1 整合素）和 JNK 显着降低，而 ERK 升高。与MTX组相比，托珠单抗组的CD20（B淋巴细胞）显着降低。接受托珠单抗治疗的患者中 IL-6 被完全阻断。两组患者滑膜间质细胞中TNF-α的表达相似。 MMP-3和CD68在滑膜表面也有类似表达。两组中 VEGF 的表达均较低。这些发现表明，与 MTX 治疗相比，MAPK 中 CD20、CD29 和 JNK 的抑制可能与托珠单抗治疗 RA 的疗效有关。
To investigate the histological changes of mitogen-activated protein kinase (MAPK) in synovium with tocilizumab in rheumatoid arthritis (RA), synovial tissue samples were assessed from ten methotrexate (MTX)-treated RA patients for control and ten tocilizumab with MTX-treated RA patients. The synovium was observed using hematoxylin and eosin (H&E) stain and analyzed immunohistochemically for the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), CD4 (T cell), CD20 (B cell), CD68 (macrophage), vascular endothelial growth factor (VEGF), CD29 (beta-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK [extracellular signal-regulated kinase (ERK) 1/ERK2], and phospho-c-Jun N-terminal kinase (JNK). H&E staining showed that there is a significant difference of cell proliferation; however, there is no change of hypervascularity in the synovium between both groups. An immunohistochemical examination showed that the decrease of CD29 (beta-1 integrin) and JNK was found significant, while ERK was increased in the tocilizumab group. CD20, B-lymphocyte, was decreased in the tocilizumab group compared with the MTX group significantly. IL-6 was completely blocked in the patients who received tocilizumab. TNF-alpha was similarly expressed in the interstitial cells of synovium of patients in both groups. MMP-3 and CD68 were similarly expressed on the surface of synovium. VEGF was less expressed in both groups. These findings indicate that the inhibition of CD20, CD29, and JNK in MAPK may be involved in the efficacy of tocilizumab compared with MTX treatment in RA.