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Structure and Functions of an IL-1 inhibitor found at inflammatory site in rabbit.

Research Project

Project/Area Number 03454172
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionKUMAMOTO UNIVERSITY

Principal Investigator

YOSHINAGA Masaru  Kumamoto University School of Medicine, Department of Pathology Professor, 医学部, 教授 (90040196)

Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1992: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥4,300,000 (Direct Cost: ¥4,300,000)
KeywordsIL-1 / IL-1 receptor antagonist / Inflammation / Inflammatory exudate cells / neutrophils / Anti-inflammatory agent / インターロイキン1レセプターアンダゴニスト / Interleukin 1 / Interlukin 1 receptor antagonigt / 炎症抑制物質
Research Abstract

A rabbit interleukin-1 (IL-1) inhibitor in inflammatory peritoneal exudate cells was purified to apparent homogeneity. This inhibitor was extracted from exudate cells of the 24-hr stage of peritoneal inflammation and purified using isoelectrofocusing (IEF), gel filtration, followed in this order by high-performance liquid chromatography steps with hydroxylapatite and anionic ion exchanger. The purified factor showed a single band on silver-stained SDS-PAGE. This molecule of MW 19 kD and pI 5.5 inhibited the binding of both IL-1alpha and beta to receptors on a thymoma cell line, EL-4 and a B-cell line, 70Z/3. We determined its primary structure by a combination of peptide chemistry and molecular cloning. The inhibitor was synthesized as a precursor composed of 177 amino acids and was processed to a mature molecule of 143 amino acids. The N-terminal amino acid of the mature inhibitor was N-acetyl-methionine residue. The deduced amino acid sequence of the inhibitor showed a 77% homology t … More o the human IL-1 receptor antagonist (IL-1ra) and essentially the same mode of action as seen with human IL-1ra. We consider the this inhibitor is a rabbit counterpart of human IL-1ra, although there are differences with respect to the molecular structure; the N-terminus of the mature rabbit IL-1ra at a position of nine amino acids downstream from that of human IL-1ra.
Further, we made a recombinant rabbit IL-1ra (rrIL-1ra) expressed in E. coli. Using the rrIL-1ra, we also made a sheep anti-serum and developed an ELISA system for the rabbit IL-1ra. The rrIL-1ra was purified using DEAE-cellulose and Sephadex G-75, in a conventional chromatography system, followed by a linear NaCl gradient-elution of DEAE-cellulose in an FPLC system. Its specific biologic activity was almost the same as the authentic natural product. Using the above described tools, we examined the generation of IL-1ra during the course of LPS-arthritis in rabbits. Production of IL-1ra peaked at 9 hr (196.7 ng/joint) and the amount was 180-200 fold molar excess of IL-1 found at the lesion, and a large amount of IL-1ra was sustained for one week. The LPS-induced arthritis was strongly suppressed by intra-articular injection of 10 mug of IL-1ra when the severity of arthritis was monitored by the infiltration of leukocytes and destruction of articular cartilage. Then, we concluded that IL-1ra play an regulatory role in inflammation and may become a potent anti-inflammatory agent. Less

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Saita N,Ando M,Araki S and Yoshinaga M: "Fibroblars proliferation pulmonary granuloma induced by Trichosporon cutaneum in rabbits:Presence of a lymphocyte derived fibroblast prolofcration factor and its functional specificity." Int.Arch.Allergy Appl.Immunol.95. 294-302 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hashimoto M,Ishikiwa Y,Yokota S,Goto F,Yoshinaga M,Bando T,Sakakibara Y and Iriki M: "Action site of circulating interleukin-1 on the rabbit brain." Brain Res. 540. 217-223 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ohkawara S,Matsukawa A and Yoshinaga M: "Neutrophils as the major producer of interleukin 1 and its inhibitor at the inflammatory site in rabbits." Archiv.Immunol.Therap.Exp.40. 11-16 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Goto F,Goto K,Miyata T,Ohkawara S.,Takao T,Mori S,Furukawa S,Maeda T,Iwanaga S,Shimonishi Y and Yoshinaga M: "Interlcukin-1 rcceplor antagonist in inflammatory cells of rabbits. Production,purification and detemination of promary structure." Immunology. 77. 235-244 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsukawa A, Mori S, Ohkawara S, Maeda T, Tanase S, Edamitsu S, Yanagi Fand Yoshinaga M: "Production,purification and characterization of a rabbit recombinant IL-1 receptor antagonist." Biomed.Res.13. 269-277 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsukawa A, Ohkawara S, Maeda T, Takagi K and Yoshinaga M: "Production of interleukin-1 and interleukin-1 receptor antagonist and the pathological significance in lipopolysaccharide-induced arthritis in rabbits." J.Clin.Exp.Immunol.(1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsukawa A,Ohkawara S and Yoshinaga M: "Intractable vasculitis syndromes" Hokkaido University Press, 131-138 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 松川 昭博、吉永 秀: "Annual Review免疫" 中外医学社, 110-117 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Saita N, Ando M, Araki S and Yoshinaga M: "Fibroblast proliferation factors in pulmonary granuloma induced by Trichosporon cutaneum in rabbits: presence of a lymphocyte derived Fibroblast proliferation factor and its functional specificity." Int. Arch. Allergy Appl. Immunol.95. 294-302 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hashimoto M, Ishikawa Y, Yokota S, Goto F, Yoshinaga M, Bando t, Sakakibara Y and Iriki M: "Action site of circulating interleukin-1 on the rabbit brain." Brain Res. 540. 217-223 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ohkawara S, Matsukawa A and Yoshinaga M: "Neutrophils as the major producer of interleukin 1 and its inhibitor at the inflammatory site in rabbits." Archiv. Immunol. Therap. Exp.40. 11-16 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Goto F, Goto K, Miyata T, Ohkawara S., Takao T, Mori S, Furukawa S, Maeda T, Iwanaga S, Shimonishi Y and Yoshinaga M: "Interleukin-1 receptor antagonist in inflammatory exudate cells of rabbits. Production, purification and determination of primary structure." Immunology. 77. 235-244 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsukawa A, Mori S, Ohkawara S, Maeda T, Tanase S, Edamitsu S, Yanagi F and Yoshinaga M: "Production, purification and characterization of a rabbit recombinant IL-1 receptor antagonist." Biomed. Res.13. 269-277 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsukawa A, Ohkawara S, Maeda t, Takagi K and Yoshinaga M: "Production of interleukin-1 receptor antagonist and the pathological significance in lipopolysaccharide-induced arthritis in rabbits." J. Cline. Exp. Immunol. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsukawa A, Ohkawara S and Yoshinaga M: Hokkaido University Press. Intractable vasculitis syndromes, 131-138 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ohkawara S, Matsukawa A and Yoshinaga M: "Neutrophils as the major producer of interleukin 1and its inhibitor at the inflammatory site in rabbits." Archiv.Immunol.Therap.Exp.40. 11-16 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Goto F,Goto K,Miyata T,Ohkawara S.,Takao T,Mori S,Furukawa S,Maeda T,Iwanaga S,Shimonishi Y and Yoshinaga M: "Interleukin-1 receptor antagonist in inflammatory exudate cells of rabbits.Production,purification and determination of primary structure." Immunology. 77. 235-244 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsukawa A, Mori S,Ohkawara S, Maeda T, Tanase S, Edamitsu S,Yanagi F and Yoshinaga M: "Production,purification and characterization of a rabbit recombinant IL-1 receptor antagonist." Biomed.Res.13. 269-277 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsukawa A,Ohkawara S,Maeda T,Takagi K and Yoshinaga M: "Production of interleukin-1 and interleukin-1 receptor antagonist and the pathological significance in lipopolysaccharide-induced arthritis in rabbits." J.Clin.Exp.Immunol.(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsukawa A,Ohkawara S and Yoshinaga M: "Intractable vasculitis syndromes" Hokkaido University Press, 131-138 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 松川 昭博、吉永 秀: "Annual Review免疫" 中外医学社, 110-117 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] F.Goto,K.Goto.,T.Miyata,S.Ohkawara,T.Takao,S.Mori,S.Iwanaga,M.Yoshinaga: "Interleukin 1 receptor antagonist in inflammatory exudate cells of rabbits.Production,purification and determination of primary structure." Immunology.

    • Related Report
      1991 Annual Research Report
  • [Publications] A.Matsakawa,S.Mori,S.Ohkawara,T.Maeda,M.Yoshinaga: "Production,purification and characterization of a rabbit recomlainant ILー1 recepton antagonist."

    • Related Report
      1991 Annual Research Report
  • [Publications] N.Satita,M.Ando,S.Araki,M.Yoshinaga: "Fibnoflast proliferation factors in rabbits:presence of a lymphocyte derived fibioblast proliferation factor and its functional specificity." International A rchives of Allergg and Applieel Immunology. 95. 284-302 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Hashimoto,Y.Ishikawa.S.Yokota,T.Bando,Y.Sakakibara,M.Iriki: "Action site of circulating interleukin 1 on the rabbit brain." Brain Research. 540. 217-223 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Sagara,S.Mori,S.Ohkawara,F.Goto,K.Takagi,M.Yoshinaga: "A limited role of ILー1 in immune enlancewent by acijavants." Immunology. 71. 251-257 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] O.Rawilo,X.SaezーLlanens,J.Mertsola,M.Yoshinaga,S.Ohkawara,G.H.McCacken: "Tumor necrosis foctor α/cachectin and interleukin 1 β initiate meuingeal inflawwation." Journal of Experimental Medicine. 172. 497-507 (1990)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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