Expression of interleukin-22 in rheumatoid arthritis - Potential role as a proinflammatory cytokine
Expression of interleukin-22 in rheumatoid arthritis - Potential role as a proinflammatory cytokine
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DOI：
10.1002/art.20965
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发表时间：
2005-04-01
影响因子：
--
通讯作者：
Nojima, Y
中科院分区：
文献类型：
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作者：
Ikeuchi, H;Kuroiwa, T;Nojima, Y
白细胞介素-22（IL-22）是IL-10家族中的一种新的细胞因子。虽然其病理生理功能在很大程度上是未知的，诱导急性期反应的IL-22已建议促炎特性。在这项研究中，我们试图研究IL-22是否在类风湿关节炎（RA）的发病机制中发挥作用。采用逆转录聚合酶链反应（RT-PCR）、Western blot和免疫组化方法检测IL-22和IL-22 R1的表达。采用Alamer blue法和酶联免疫吸附法检测重组IL-22（rIL-22）对RA患者滑膜成纤维细胞（RASF）增殖和单核细胞趋化蛋白1（MCP-1）产生的影响。采用RT-PCR方法检测RA滑膜组织和RA滑液中单个核细胞中IL-22 mRNA的表达。IL-22在RA滑膜组织的衬里层和衬里下层均呈高水平表达。分别作为滑膜成纤维细胞和巨噬细胞标志物的波形蛋白和CD 68染色显示，大多数IL-22阳性细胞是滑膜成纤维细胞和巨噬细胞。IL-22 R1在RA滑膜组织的衬里层和衬里下层也有表达。大多数表达IL-22 RI的细胞对波形蛋白呈阳性，但对CD 68不呈阳性。RT-PCR和Western blot分析证实RASF中IL-22和IL-22 R1的表达。在体外，rIL-22显著增加RASF的增殖和由RASF产生的MCP-1高于培养基对照值。此外，IL-22刺激RASF可诱导MAPK活化。这些数据表明，由滑膜成纤维细胞和巨噬细胞产生的IL-22通过诱导滑膜成纤维细胞的增殖和趋化因子产生来促进RA滑膜组织中的炎症反应。
Interieukin-22 (IL-22) is a novel cytokine of the IL-10 family. Although its pathophysiologic function is largely unknown, induction of acute-phase responses by IL-22 has suggested proinflammatory properties. In this study, we sought to examine whether IL-22 plays a role in the pathogenesis of rheumatoid arthritis (RA).Methods. Expression of IL-22 and IL-22 receptor I (IL-22R1) was examined by reverse transcriptionpolyinerase chain reaction (RT-PCR), Western blot, and immunohistochemical analysis. The effects of recombinant IL-22 (rIL-22) on cultured synovial fibroblasts derived from RA patients (RASF), with regard to the proliferation of synovial fibroblasts and production of monocyte chemoattractant protein 1 (MCP-1), were examined by alamer blue assay and enzyme-linked immunosorbent assay, respectively.Results. IL-22 messenger RNA was detected by RT-PCR in RA synovial tissues and mononuclear cells isolated from RA synovial fluid samples. High levels of IL-22 were expressed both in the lining and the sublining layers of RA synovial tissues. Staining for vimentin and CD68, as markers of synovial fibroblasts and macrophages, respectively, showed that the majority of IL-22-positive cells were synovial fibroblasts and macrophages. IL-22R1 was also expressed in both the lining and the sublining layers of RA synovial tissues. The majority of cells expressing IL-22RI were positive for vimentin, but not for CD68. Expression of IL-22 and IL-22R1 in RASF was confirmed by RT-PCR and Western blot analysis. In vitro, rIL-22 significantly increased proliferation of RASF and production of MCP-1 by RASF above the value of medium controls. Moreover, MAPK activation was induced in RASF in response to IL-22 stimulation.Conclusion. These data suggest that IL-22, produced by synovial fibroblasts and macrophages, promotes inflammatory responses in RA synovial tissues by inducing the proliferation and chemokine production of synovial fibroblasts.