Expression of interleukin-19 in synovial tissue from patients with rheumatoid arthritis

类风湿性关节炎患者滑膜组织中白细胞介素19的表达

• 批准号: 06670485
• 负责人: YAMAMURA Masahiro
• 金额: $ 1.54万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670485/
• 关键词: rheumatoid arthritis; interleukin-10; interleukin-4; interleukin-13; anti-inflammatory cytokine; inflammatory cytokine; macrophages; T cells; 滑膜; インターフェロン-γ; リウマトイド因子; 変形性関節症; インターロイキン-10(IL-10); 滑膜病変部; RT-PCR法; サイトカイン・ネットワーク

The expression of interleukin-10 and its pathogenic role in rheumatoid arthritis (RA) was investigated. Concentrations of IL-10 in both serum and synovial fluid from RA patients were greater compared to those of osteoarthritis patients. Synovial tissues in RA more strongly expressed IL-10 mRNA than in OA, and spontaneously produced higher levels of IL-10. By Immunohistochemical staining and detection of IL-10 in isolated macrophages, fibroblasts, and T cells from RA synovium, macrophages in both the lining and sublining layer are major sources of this cytokine. IL-10 markedly inhibited the production of inflammatory cytokines such as IL-1 and TNF-α by RA synovium, but both cytokines were potent inducer of IL-10. On the other hand, T cell-derived anti-inflammatory cytokines, IL-4 and Il-13, are less efficient in inhibiting synovial inflammatory cytokines, 7but are able to inhibit proliferation of RA synovial fibroblasts. However, their expression in RA joint is extremely limited IL-10 expression was associated with levels of IgG-rheumatoid factor in RA. These results indicate that IL-10 may be mostly responsible for downregulation of chronic inflammation and rheumatoid factor production in RA, although its synoival expression if not sufficient to control the disease activity.Of IL-6-type cytokines, large amounts of IL-6, IL-11, and LIF were produced mainly by IL-1 or TNF-activated fibroblasts, whereas oncostatin M was exclusively by macrophages in RA joints. However, only IL-6 was circulating at significant levels in association with raised levels of serum CRP levels, indicating its contribution to systemic inflammatory reactions such as acute-pahse reactant production by liver.

研究了白细胞介素 10 的表达及其在类风湿性关节炎 (RA) 中的致病作用。 RA 患者血清和滑液中 IL-10 的浓度高于骨关节炎患者。 RA 滑膜组织比 OA 更强烈地表达 IL-10 mRNA，并且自发产生更高水平的 IL-10。通过免疫组织化学染色和检测 RA 滑膜中分离的巨噬细胞、成纤维细胞和 T 细胞中的 IL-10，发现内衬层和亚衬层中的巨噬细胞是该细胞因子的主要来源。 IL-10显着抑制RA滑膜产生炎症细胞因子如IL-1和TNF-α，但这两种细胞因子都是IL-10的有效诱导剂。另一方面，T 细胞衍生的抗炎细胞因子 IL-4 和 Il-13 在抑制滑膜炎性细胞因子方面效果较差，7 但能够抑制 RA 滑膜成纤维细胞的增殖。然而，它们在 RA 关节中的表达极其有限 IL-10 的表达与 RA 中 IgG 类风湿因子的水平相关。这些结果表明，IL-10 可能是 RA 中慢性炎症和类风湿因子产生下调的主要原因，尽管其滑膜表达不足以控制疾病活动。在 IL-6 型细胞因子中，大量 IL-6、IL-11 和 LIF 主要由 IL-1 或 TNF 激活的成纤维细胞产生，而制瘤素 M 专门产生。 由 RA 关节中的巨噬细胞引起。然而，只有 IL-6 的循环水平显着，且与血清 CRP 水平升高相关，表明其对全身炎症反应（例如肝脏产生的急性期反应物）有贡献。

项目成果

Masahiro Yamamura, Hirofumi Makino: "Cytokine expression of rheumatoid arthritis"Igakuno-ayumi. 182(9). 573-578 (1997)

Masahiro Yamamura、Hirofumi Makino：“类风湿性关节炎的细胞因子表达”Igakuno-ayumi。

Yoshitaka Morita, Masahiro Yamamura, Tetsushi Aita, Masanori Kawashima, Seishi Harada, Hideyuki Okamoto, Hajime Inoue, Hirofumi Makino: "Differential Effects of IL-4, IL-10 and IL-13 on Proinflammatory Cytokine Production and Fibroblast Proliferation in V

Yoshitaka Morita、Masahiro Yamamura、Tetsushi Aita、Masanori Kawashima、Seishi Harada、Hideyuki Okamoto、Hajime Inoue、Hirofumi Makino：“IL-4、IL-10 和 IL-13 对 V 中促炎细胞因子产生和成纤维细胞增殖的不同影响

H,Okamoto.M,Yamamura.Y,Ohmoto.et al.: "Increased production of interleukin-6,leukemia inhibitory factor,and oncostatin M by synovial tissue of rheumatoid arthritis"Arthritis Rheum. 37(9). S382-382 (1994)

H，Okamoto.M，Yamamura.Y，Ohmoto.et al.：“类风湿性关节炎滑膜组织增加白细胞介素 6、白血病抑制因子和制瘤素 M 的产生”关节炎大黄。

Kazuhiko Ezawa, Masahiro Yamamura, Hideyuki Okamoto, Zensuke Ota, Hirofumi Makino: "Comparative analysis of CD45RA-and CD45ro-positive CD4ィイD1+ィエD1T cells in peripheral blood, synovial fluid, and synovial tissue in patients with rheumatoid arthritis and a

Kazuhiko Ezawa、Masahiro Yamamura、Hideyuki Okamoto、Zensuke Ota、Hirofumi Makino：“类风湿性关节炎和关节炎患者外周血、滑液和滑液组织中 CD45RA 和 CD45ro 阳性 CD4D1+D1T 细胞的比较分析

Masahiro Yamamura, Hirofumi Makino: "Cytokine expression of rheumatoid arthritis"Clin Immunol. 29(12). 1495-1503 (1997)

Masahiro Yamamura、Hirofumi Makino：“类风湿性关节炎的细胞因子表达”Clin Immunol。