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Molecular analysis of anti-inflammatory effect of IL-10 and IL-4 on human monocytes

Research Project

Project/Area Number 07671213
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKyushu University

Principal Investigator

OTSUKA Takeshi  Kyushu University, Faculty of Medicine, assistant professor, 医学部, 助手 (50213773)

Co-Investigator(Kenkyū-buntansha) IZUHARA Kenji  National Institute of Genetics, assistant professor, 助手 (00270463)
TANAKA Yosuke  Kyushu University, 医学部, 医員
NEMOTO Yoshiaki  Kyushu University, 医学部, 医員
NIIRO Hiroaki  Kyushu University, 医学部, 医員
NAKASHIMA Hitoshi  Kyushu University, Faculty of Medicine, assistant professor, 医学部, 助手 (70188960)
空閑 聖治  九州大学, 医学部, 医員
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Keywordsmonocyte / macrophage / interleukin-4 / interleukin-10 / cyclooxygenase / JAK / STAT / signal transduction / シクロキシゲナーゼ / 炎症制御
Research Abstract

1.IL-4 suppressed and IL-10 rather enhanced NO by mouse monocytic cell lines. Production of TNF-a or superoxide anions were suppressed by both IL-4 and IL-10, indicating that regulatory mechanism of NO production is not regulated by TNF-a production alone. Macrophage cell lines expressing human IL-4 receptor alpha chain on the cell membrane, were suppressed NO and TNF-alpha by human IL-4.
2.Mouse resident (RPMf) and thioglycollate-elicited (TPMf) peritoneal macrophages released a substantial amount of NO after stimulation with LPS or a combination of LPS and IFN-g (LPS/IFN-g). Both IL-10 and IL-4 inhibitedNO production by stimulated TPMf. On the other hand, NO production by stimulated RPMf was inhibited by IL-4, but was enhanced by IL-10.
3.We examined the activation of STAT molecules by using electrophoretic mobility-shift assayusing (EMSA). Using a DNA probe corresponding to a GAS-motif sequence conserved in the promoter region of cyclooxygenase (COX) -2 genes for human, mouse and rat, STAT5 was shown to be activated in human peripheral monocytes stimulated with LPS.This activation of STAT5 was neutralized partly by an antibody against GM-CSF.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Niiro H 外: "Regulation by IL-10 and IL-4 of inducible cyclooxygenase (COX-2) expression in human ncutrephils" Blood. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Niho Y 外: "Role of IL-10 in the crossregulation of prostaglandins and cytokines in ironocytes" Mol.Biol.Hem.(印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Asano Y 外: "Effect of (-)-EpigallocatechinGallate on Leukemic Blast Cells from, Patients with Acute Myeloblastic-Leukemia" Life Science. 60(2). 135-142 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Izuhara K 外: "Signal transduction pathway of iuterleukiu-4 and interleulcin-13 in human B cells deriveol from X-liuked sovere conbineol hnmuno deficiency patients" J.Biol.Chem. 271. 619-622 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kuga S 外: "Suppression of Superoxide Anion Production by Interleukin-10 is Accompanied by a Down-Regulation of the Genes for Subunit Proteins of Nadph Oxidase" Experimental Hematology. 24. 151-157 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka Y 外: "Effect of lnterleukin-10 on collagen-induced arthrits in micc" Inflammation Research. 45. 283-288 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nemoto Y,Otsuka T,Niiro H Kuga S,Tanaka Y,Nakashima H,Niho Y: "Inhibitory effects of interleukin (IL) -10 and viral IL-10 (vIL-10) on the functions of monocytes/macrophages." Jpn.J.Clin.Immunol. 18. 152-159 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Xu LX,Kukita T,Kukita A,Otsuka T,Niho Y,Iijima T: "Interleukin 10 selectively inhibits osteoclastogenesis by inhibiting differentiation of osteoclast progenitors into preosteoclast-like cells in rat bone marrow culture system." J.Cell Physiol. 165. 624-629 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Niiro H,Otsuka T,Tanabe T,Hara S,Kuga S,Nemoto Y,Tanaka Y,Nakashima H,Abe M,Niho Y: "Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes : Its underlying mechanism in comparison with interleukin-4." Blood. 85(12). 3736-3745 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Izuhara K,Ideguchi H,Otsuka T,Okubo K,Oga T,Hamasaki N,Niho Y: "incidence of a polymorphic variant of erythrocyte membrane protein, Band 3-Memphis, on a western Japanese island." Jpn.J.Hum.Genetics High. 40(3). 265-270 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Izuhara K,Heike T,Otsuka T,Yamaoka K,Mayumi M,Imamura T,Niho Y,Harada N: "Signal Transduction Pathway of Interleukin-4 and Interleukin-13 in Human B Cells Derived from X-linked Severe Combined Immunodeficiency Patients." J.Biol.Chem.vol.271. 619-622 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kuga S,Otsuka T,Niiro H,Nunoi H,Nemoto Y,Nakano T,Ogo T,Niho Y: "Suppression of superoxide anion production by interleukin-10 is accompanied with a downregulation of the genes for subunit proteins of NADPH oxidase." Exp.Hematol.24. 151-157 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka Y,Otsuka T,Hotokebuchi T,Miyahara H,Nakashima H,Kuga S,Nemoto Y,Niiro H,Niho Y: "Effect of IL-10 on collagen-induced arthritis in mice." Inflam.Res.45. 283-288 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Niho Y,Niiro H,Otsuka T: "Role of IL-10 in the crossregulation of prostaglandins and cytokines in monocytes." Mol.Biol.Hem.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Niiro H,Otsuka T,Izuhara K,Yamaoka K,Ohshima K,Tanabe T,Hara S,Nemoto Y,Tanaka Y,Nakashima H,Niho Y: "Regulation by interleukin-10 and interleukin-4 of cyclooxygenase-2 expression in human neutrophils" Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nemoto Y,Otsuka T,Niiro H,Izuhara K,Tanaka Y,Kuga S,Nakashima H,Niho Y: "Differential effect of interleukin-10 on nitric oxide production by resident and elicited murine peritoneal macrophages." (submitted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Izuhara K,Sakai M,Inaba R,Imamura T,Otsuka T,Niho Y,Heike T,Harada N: "Signal transduction passway of interleukin-4 and interleukin-13 in human B cells derived from X-linked severe combined immunodeficiency patients." 40th annual meeting of the Japan Society of Human Genetics, Kumamoto. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Niiro H,Otsuka T,Kuga S,Nemoto Y,Tanaka Y,Nakashima H,Niho Y: "Inhibition by IL-10 of inducible cyclooxygenase expression in LPS-stimulated monocytes : Its underlying mechnism in comparison with IL-4." The 9th International Congress of Immunology San Francisco. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nemoto Y,Otsuka T,Nakashima H,Tanaka Y,Kuga S,Niiro H,Niho Y: "Differential effect of IL-10 on nitric oxide production by resident and elicited murine peritoneal macrophages : Its effect in comparison with IL-4." The 9th International Congress of Immunology San Francisco. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Niiro H 外: "Regulation by IL-10 and IL-4 of inducible cyclooxygenase(COX-2)expression in human rcutrephils" Blood. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Niho Y 外: "Role of IL-10 in the crossregulation of prostaglandins and cytokines in ironocytes" Mol.Biol.Hem.(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Asano Y 外: "Effect of(-)-epigallocatechin gallate on leukemic blast Cells from patients with acute myeloblastic lcukemia" Life Science. 60(2). 135-142 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Izuhara K 外: "Signal transduction pathway of interleukin-4 and interleukin-13 in human B cells derived from X-linked severe conbineol immuno deficiency patients" J.Biol.Chem. 271. 619-622 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kuga S 外: "Suppression of superoxide anion production by interleukin-10 is accompanied with a down regnlation of the genes for subunit proteins of NADPH oxidase" Experimental Hematology. 24. 151-157 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka Y 外: "Effect of interleukin-10 on collagen-induced arthritis in mice" Inflamation Resarch. 45. 283-288 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Izuhara K.外: "Signal transdnetror pathcuay of intertenkin-4 and in terlenk in -13 in humin B cells derived from X-liuked severe comliual immunodeficieney patieuts" J.Biol.Chem.271. 619-622 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kuga S.外: "Suppression of supuroxide anion production by interkukin-10 is accempahied with a diumregulation of the gehes subunit proteins of NADPH oxidase" Exp.Hematology. 印刷中. (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Niiro H.外: "Inhibition by interleukin-10 of induable cycloxygenase expresion in lpcplyeulaid stiunlated monocytes: Its underlyirg mechanism in comparson with interlenlin-4" Blood. 85. 3736-3745 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Xu LX.外: "Interleukin-10 seleitively inlubitsosteoclastogenesis by imhibiting diffeventnlron of osteoclast poogenstcrsinto predstetclait-like cells in rat bone mairow cutture systen." J.Cell.Phystol.165. 624-629 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nemoto Y.外: "Inhibitery effects of interlenkin (IL) -10 and viral IL-10 (VIL-10) on the functions of mahcytes/mcairephates." Jpn.J.Clin.lmmunol.18. 152-159 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Izuhara K.外: "Higy incrdence of a polywarphic variant of erythrocyte membrane protein, Band-3-Memphis on a western Japanes rsland." Jpn.J.Hum.Genetics. 40. 265-270 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 空閑聖治 外: "Annual Review 免疫" IL-10のマクロファージ機能抑制機序, 12 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 大塚 毅: "医学のあゆみ" 免疫疾患と抗サイトカイン療法, 4 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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