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

Research Project

Project/Area Number 06670485
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionOkayama University

Principal Investigator

YAMAMURA Masahiro  Okayama University, Medical School, Associate Professor, 医学部, 助教授 (80252956)

Co-Investigator(Kenkyū-buntansha) SHIKATA Ken-ichi  Okayama University, Medical School, Assistant Professor, 医学部, 講師 (00243452)
KASHIHARA Naoki  岡山大学, 医学部・附属病院, 講師 (10233701)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsrheumatoid 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
Research Abstract

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.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (46 results)

All Other

All Publications (46 results)

  • [Publications] M,Yamamura.H,Okamoto.S,Harada.et al.: "Interleukin-10 expressed in synovial tissue modulates the cytokine profile of rheumatoid arthritis"Arthritis Rheum. 37(9). S309-309 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S,Harada.M,Yamamura.H,Okamoto.et al.: "Differential effects,of interleukin-4 and interleukin-10 on theumatoid synovial fibroblasts"Arthritis Rheum. 37(9). S381-381 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H,Hashimoto.M,Yamamura.K,Nishiya.et al.: "Impaired interleukin-8 dependent chemotaxis by synovial fluid polymorphonuclear leukocytes in rheumatoid arthritis"Acta Medica Okayama. 48(4). 181-187 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y,Morita.M,Yamamura.S,Harada.et al.: "Anti-inflammatory properties of interleukin-13 in rheumatoid synovial inflammation"Arthritis Rheum. 38(9). S353-353 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H,Okamoto.M,Yamamura.N,Kashihara.et al.: "Constitutive activation of NF-kB in rheumatoid synovium"Arthritis Rheum. 38(9). S353-353 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Yamamura.Y,Morita.H,Okamoto.et al.: "The expression of interleukin-12 as an inducer of T helpher type 1-specific immune responses in rheumatoid synovitis"Arthritis Rheum. 38(9). S354-354 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Harada.M,Yamamura.H,Okamoto.et al.: "Interleukin-7 production by rheumatoid synovial fibroblasts"Arthritis Rheum. 38(9). S355-355 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 山村昌弘: "CD8+Th2細胞とサプレッサーT細胞との関連"臨床免疫. 28(2). 245-249 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 原田誠之、山村昌弘、岡本英之、他: "慢性関節リウマチ滑膜線維芽細胞によるIL-7の産生"医学のあゆみ. 178(6・7). 435-436 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 岡本英之、山村昌弘、守田吉孝、他: "慢性関節リウマチ滑膜細胞における活性化NF-KBの構成的発現"医学のあゆみ. 179(2). 167-168 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 山村昌弘、岡本英之、原田誠之、他: "サイトカイン発現からみた慢性関節リウマチ(RA)の病因・病態の成立機構:RAはTh1 cell-mediated autoimmune diseaseか?"Biotherapy. 10(10). 1267-1271 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K,Ezawa.M,Yamamura.H,Matsui.et al.: "Comparative analysis of CD45RA-and CD45RO-positive CD4+T cells in peripheral blood,synovial fluid,and synovial tissue in patients with rheumatoid arthritis and osteoarthritis"Acta Medica Okayama. 51(1). 25-31 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H,Okamoto.M,Yamamura.Y,Morita.et al.: "The synovial expression and serum levels of interleukin-6,interleukin-11, leukemia inhibitory factor,and oncostatin M in rheumatoid arthritis"Arthritis Rheum. 40(6). 1096-1105 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y,Morita.M,Yamamura.N,Kashihara.et al.: "Increased production of interleukin-10 and inflammatory cytokines in blood monocytes of hamodialysis patients"Res.Commun.Mol.Pathol.Pharmacol.. 98. 19-33 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 山村昌弘、槙野博史: "慢性関節リウマチ滑膜におけるサイトカイン発現異常"医学のあゆみ. 182(9). 573-578 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 山村昌弘、槙野博史: "慢性関節リウマチ滑膜からのサイトカイン産生異常"臨床免疫. 29(12). 1495-1503 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y,Morita.M,Yamamura.T,Aita.et al.: "Differential Effects of IL-4、IL-10 and IL-13 on Pro-inflammatory cytokine Production and Fibroblast Proliferation in Vitro in Rheumatoid Synovium"International Rheumatol. (in revision).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahiro Yamamura, Hideyuki Okamoto, Seishi Harada, Yoshitaka Morita, Takako Miura, Zensuke Ota: "Interleukin-10 expressed in synovial tissue modulates the cytokine profile of rheumatoid arthritis."Arthritis Rheum. 37(9). s309 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Seishi Harada, Masahiro Yamamura, Hideyuki Okamoto, Yoshitaka Morita, Takako Miura, Zensuke Ota: "Differential effects of interleukin-4 and interleukin-10 on rheumatoid synovial fibroblasts."Arthritis Rheum. 37(9). s381 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideyuki Okamoto, Masahiro Yamamura, Yasuichi Ohmoto, Zensuke Ota: "Increased production of interleukin-6, leukemia inhibitory factor, and oncostatin M by synovial tissue of rheumatoid arthritis"37(9). s382 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiroo Hashimoto, Masahiro Yamamura, Koji Nishiya, Zensuke Ota: "Impaired interleukin-8-dependent chemotaxis by synovial fluid polymorphonuclear leukocytes in rheumatoid arthritis."Acta Medica Okayama. 48(4). 181-187 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshitaka Morita, Masahiro Yamamura, Seishi Harada, Hideyuki Okamoto, Chikage Takahar, Zensuke Ota: "Anti-inflammatory properties of interleukin-13 in rheumatoid synovial inflammation"Arthritis Rheum. 38(9). s353 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideyuki Okamoto, Masahiro Yamamura, Naoki Kashihara, Seishi Harada, Yoshitaka Morita, Chikage Takahara, Zensuke Ota: "Constitutive activation of NF-kB in rheumatoid synovium"Arthritis Rheum. 38(9). s353 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahiro Yamamura, Yoshitaka Morita, Hideyuki Okamoto, Seishi Harada, Chikage Takehara, Yasuyo Sakata, Yasukazu Ohmoto, Robert L. Modlin, Zensuke Ota: "The expression of interleukin-12 as an inducer of T helper type 1-specific immune responses in rheumatoid synovitis."Arthritis Rheum. 38(9). s354 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Seishi Harada, Masahiro Yamamura, Hideyuki Okamoto, Yoshitaka Morita, Chikage Takehara, Zensuke Ota: "Interleukin-7 production by rheumatoid synovial fibroblasts."Arthritis Rheum. 38(9). s355 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahiro Yamamura: "CD8ィイD1+ィエD1Th2 cells and suppressor T cells"Clin Immunol. 28(2). 245-249 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Seishi Harada, Masahiro Yamamura, Hideyuki Okamoto, Yoshitaka Morita, Hirofumi Makino: "Interleukin-7 production by synovial fibroblasts from patients with rheumatoid arthritis."Igakuno-ayumi. 178(6/7). 435-436 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideyuki Okamoto, Masahiro Yamamura, Naoki Kashihara, Seishi Harada, Yoshitaka Morita, Takano Miura, Chikage Takehara, Masanori Kawashima, Hirofumi Makino: "Constitutive activation of activated NF-kB in synovial tissues from patients with rheumatoid arthritis."Igakuno-ayumi. 179(2). 167-168 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahiro Yamamura, Hideyuki Okamoto, Seishi Harada, Yoshitaka Morita, Hirofumi Makino: "Cytokine expression in rheumatoid synovium: Is rheumatoid arthritis a Th1 cell-mediated autoimmune disease?"Biotherapy. 10(10). 1267-1271 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 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 arthritis and osteoarthritis."Acta Med Okayama. 51(1). 25-31 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideyuki Okamoto, Masahiro Yamamura, Seishi Harada, Yoshitaka Morita, Hirofumi Makino, Zensuke Ota: "The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostain M in rheumatoid arthritis."Arthritis Rheum. 40(6). 1096-1105 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshitaka Morita, Masahiro Yamamura, Naoki Kashihara, Hirofumi Makino: "Increased production of interleukin-10 and inflammatory cytokines in blood monocytes of hemodialysis patients"Res. Commun. Mol. Pathol. Pharmacol.. 98. 19-33 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahiro Yamamura, Hirofumi Makino: "Cytokine expression of rheumatoid arthritis"Igakuno-ayumi. 182(9). 573-578 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahiro Yamamura, Hirofumi Makino: "Cytokine expression of rheumatoid arthritis"Clin Immunol. 29(12). 1495-1503 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 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 Vitro in Rheumatoid Synovium"International Rheumatol. in revision.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Morita,Y.,et al.: "Anti-Inflammatory Properties of Interleukin-13 in Rheumatoid Synovial Inflammation" Arthritis & Rheumatism. 38. S353 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okamoto,H.,et al.: "Constitutive Activation of NF-KB in Rheumatoid Synovium" Arthritis & Rheumatism. 38. S353 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamamura,M.,ea al.: "The Expression of Interleukin-12 as an inducer of T Helper Type 1-Specific Immane Responses in Pheumatoid Synovitis" Arthritis & Rheumatism. 38. S354 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Harada,S.,et al.: "Interleukin-7 Production by Rheumutoid Synovial Fibroblasts" Arthritis & Rheumatism. 38. S355 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 山村 昌弘: "CD8^+Th2細胞とサプレッサーT細胞との関連" 臨床免疫. 28. 245-249 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sieling,P.A.,et al.: "IL-12regutates T helper typel cytokine responses in human infectious disease" Journal of Immunology. 153. 3639-3647 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yamamura,M.,et al.: "Interleukin-10 expressed in synorial tissue modulates the cytokine profile of rheumatoid arthritis" Arthritis and Rheumatism. 37. S306- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Harada,S.,et al.: "Different effects of interleukin-4 and interleukin-10 on rheumatoid synovial fibroblasts" Arthritis and Rheumatism. 37. S381- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Okamoto,H.,et al.: "Increased production of interieukin-6.leukemia inhibitory factor,and oncostatin M by synovial tissue of rheumatoid arthritis" Arthritis and Rheumatism. 37. S382- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hashimoto,H.,et al.: "Impaired in rerleukin-8-dperclent chemotaxis by synorial fhid polymorphonuclear leukacytes in rhenmatoiel arthritis" Acta Medica Okayama. 48. 181-187 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2020-01-17  

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