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The mechanism and its regulation of interleukin 1 biological activities

Research Project

Project/Area Number 11470487
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionFaculty of Pharmaceutical Sciences, Nagoya City University

Principal Investigator

ONOZAKI Kikuo  Fac. Phar. Sci., Nagoya City Univ., Professor, 薬学部, 教授 (20101313)

Co-Investigator(Kenkyū-buntansha) TAKII Takemasa  Fac. Phar. Sci., Nagoya City Univ., Assis. Professor, 薬学部, 助手 (80244573)
HAYASHI Hidetoshi  Fac. Phar. Sci., Nagoya City Univ., Asso. Professor, 薬学部, 助教授 (80198853)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsIL-1 / IL-1 receptor / cytokine / ODC / antizyme / CHOP / melanoma / TLR
Research Abstract

IL-1 plays an important role in host reactions, including immunologic, inflammatory and hematologic reactions, and in regulation of cell proliferation and differentiation. In this study we attempted to clarify (A) the mechanism of IL-1 signaling leading to the inhibition of cell proliferation of human melanoma cells A375, (B) the regulatory mechanism of expression of IL-1 receptor (IL-1R) and its family in vitro and in vivo. The following points have been clarified.
(A)
1) It was suggested that IL-1 up-regulated the protein level of AZ, a reguratory factor of ornithine decarboxylase (ODC), at translational level, and IL-1 responsive region was present within the sequence of AZ mRNA.
2) CHOP contributed to the antiproliferative effect of IL-1 by augmenting IL-6 transcription
3) CHOP augmented the transcriptional activity of many factors, including NF-IL-6, AP-1, ISRE and NF-κB.
4) CHOP also appeared to stabilize the protein levels of other C/EBP family members.
5) TNF inhibited the proliferation of both IL-1 sensitive A375-6 cells and IL-1 resistant A375-R8 cells. The p38MAPK-dependent antiproliferative pathway of TNF was observed in these two cell clones however p38MAPK-independent apoptosis pathway was observed in only R8 cells. The anti-apoptosis factor with very short half life appeared to be present in A375-6 cells but not in R8 cells.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] T.Hattori, S.Itoh, H.Hayashi, T.Chiba, T.Takii, K.Yoshizaki, K.Onozaki: "CHOP, a basic leucine zipper transcriptional factor, contributes to the antiproliferative effect of IL-1 on human melanoma cells A375 through augmenting transcnption of IL-6"J. Interferon Cytokine Res.. 21(5). 323-332 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Hattori, H.Hayashi, T.Chiba, K.Onozaki: "Activation of two distinct anti-proliferative pathways, apoptosis and p38MAP kinase-dependent cell cycle arrest, by tumor necrosis factor in human melanoma cell line A375"European Cytokine Network. 12(2). 244-252 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Takii, C.Abe, A.Tamura, S.Ramayah, J.T.Belisle, P.J.Brennan, K.Onozaki: "Interleukin 1 or tumor necrosis factor α augments the cytotoxicic effect of mycobacteria on human fibroblasts : Application to evaluation of pathogenesis of clinical isolates of M tuberculosis and M. avium complexe"J. Interferon Cytokine Res.. 21(3). 187-196 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Takii, C. Abe, A. Tamura, S. Ramayah, J. t. Belisle, P. J. Brennan, and K. Onozaki: "Interleukin 1 or tumor necrosis factor a augmented the cytotoxicic effect of mycobacteria on human fibroblasts : Application to evaluation of pathogenesis of clinical isolates of M. tuberculosis and M. avium complex"J. Interferon Cytokine Res.. 21. 187-196 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Hattori, H. Hayashi, T. Chiba, and K. Onozaki: "Activation of two distinct anti-proliferative pathways, apoptosis and p38MAP kinase-dependent cell cycle arrest, by tumor necrosis factor in human melanoma cell line A375"Eur. Cytokine Net.. 12. 244-252 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Hattori, S. Itoh, H. Hayashi, T. Chiba, T. Takii, K. Yoshizaki and K. Onozaki: "CHOP, a basic leucine zipper transcriptional factor, contributes to the antiproliferative effect of IL- 1 on human melanoma cells A375 through augmenting transcription of IL-6"J. Interferon Cytokine Res.. 21. 323-332 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Hattori, Itoh S., Hayashi H., Chiba T., Takii T., Yoshizaki K., Onozaki K.: "CHOP a basic leucine zipper transcri ptional factor, contributes to the antiproliferative effect of IL-i on human melanoma cells A375 through augmenting transcnption of IL-6"J. Interferon Cytokine Res.. 21(5). 323-332 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Hattori, H.Hayashi, T.Chiba, K.Onozaki: "Activation of two distinct anti-proliferative pathways, apoptosis and p38MAP kinase-dependent cell cycle arrest, by tumor necrosis factor in human melanoma cell line A375"European Cytokine Network. 12(2). 244-252 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Takii, C.Abe, A.Tamura, S.Ramayah, J.T.Belisle, P.J.Brennan, K.Onozaki: "Interleukin 1 or tumor necrosis factor α augmented the cytotoxicic effect of mycobacteria on human fibroblasts: Application to evaluation of pathogenesis of clinical isolates ofM. tuberculosis and M. aviurn comolexe"J. Interferon Cytokine Res.. 21(3). 187-196 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Hattori,Itoh S.,Hayashi H.,Chiba T.,Takii T.,Yoshizaki K.,Onozaki K.: "CHOP, a basic leucine zipper transcriptional factor, contributes to the antiproliferative effect of IL-1 on human melanoma cells A375 through augmenting transcription of IL-6."J.Interferon Cytokine Res.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Hattori,H.Hayashi,T.Chiba,K.Onozaki: "Activation of two distinct anti-proliferative pathways, apoptosis and p38MAP kinase-dependent cell cycle arrest, by tumor necrosis factor in human melanoma cell line A375."European Cytokine Network. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Matsumura,A.Ito,T.Takii,H.Hayashi,K.Onozaki: "Endotoxin and cytokine regulation of Toll-like receptor (TLR) 2 and TLR4 geneexpression in murine liver and hepatocytes."J.Interferon Cytokine Res.. 20(10). 915-921 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Iwase,K.Tsujimura,M.Yasue,S.Ozeki,K.Onozaki,T.Takahashi: "Comparison of anti-tumor responses against TL positive lymphoma induced by skin grafting and dendriti cell immunization."Microbiol.Immunol.. 44(7). 609-618 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Sasayama,K.Moriya,T.Chiba,T.Matsumura,H.Hayashi,A.Hayashi,K.Onozaki: "Glycosylated human interleukin-1α, neoglyco IL-1α, coupled with N-acetyl-neuraminic acid exhibits selective activities in vivo and altered tissue distribution."Glycoconjugate J.. 17(6)(in press). (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Watanabe,K.Katagiri,K.Onozaki,N.Hata,Y.Misawa,T.Hamazaki,H.Okuyama: "Dietary docosahexaenic acid but not eicosapentaenoic acid suppresses lipopoly-saccharide-induced interleukin 1 β mRNA induction in mouse spleen leukocytes."Prostagl Leukotr Essent Fatty Acids. 62(3). 147-152 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Itoh,T.Hattori,H.Hayashi,Y.Mizutani,M.Todo,T.Takii,D.Yang,J.C.Lee,S.Matsufuji,Y.Murakami,T,Chiba,K.Onozaki: "Antiproliferative effect of interleukin 1 (IL-1) is mediated by p38MAP kinase in human melanoma cells A375"Journal of Immunology. 162・12. 7434-7440 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Ito,T.Takii,T.Matsumura,K.Onozaki: "Augmentation of type I IL-1 receptor expression and IL-1 signaling by IL-6 and glucocorticoid in murine hepatocytes"Journal of Immunology. 162・7. 4260-4265 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Takii,H.Honda,S.Sasayama,T.Kobayashi,H.Ikezawa,S.Udaka,Y.Oomoto,K.Onozaki: "Human interelukin-1 receptor antagonist: large-scale expression in Bacillus brevis 47-50"Journal of Inerferon and Cytokine Research. 19・11. (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Takii,A.Ito,S.Kawashima,A.Ninomiya,T.Matsumura,H.Hayashi,K.Onozaki: "Tyrosine kinase is essential for the constitutive expression of type I interleukin 1 receptor in human fibroblast cells"European Cytokine Network. 10・2. 237-346 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Takii,M.Hayashi,H.Hiroma,T.Chiba,S.Kawashima,H.L.Zhang,A.Nagatsu,J.Sakakibara,K.Onozaki: "Serotorin derivative, N-(p-coumaroyl)serotorin, isolated from safflower (Carthamus tinctorius L) oil cake augments the proliferaton of nomal human and mouse fibroblasts in synergy with bFGF)or EGF"Journal of Biochemistry. 125・5. 910-915 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Ono,T.Takii,K.Onozaki,M.Ikawa,M.Okabe,M.Sawada: "Migration of exogenous immature hematopoietic cells into adult mouse brain parenchyma under GFP-expressing bone marrow chimera"Biochemical and Biophysical Research Communications. 262・3. 610-614 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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