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Study on function of cytokine LECT2 expressed in the liver using a mouse

Research Project

Project/Area Number 13670581
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

YAMAGOE Satoshi  National Institute of Infectious Diseases, Bioactive Molecules, Senior Researcher, 生物活性物質部, 主任研究官 (00212283)

Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsLECT2 / Cytokine / Hepatitis / Concanavalin A / concanavalin A / NKT細胞
Research Abstract

LECT2 (leukocyte cell-derived chemotaxin 2) was originally identified for its possible chemotactic activity against human neutrophils in vitro. It is a 16-kDa protein that is preferentially expressed in the liver. Its homologues have been widely identified in many vertebrates. Current evidence suggests that LECT2 may be a multifunctional protein like cytokines. However, the function of LECT2 in vivo remains unclear. To elucidate the role of this protein in vivo, we have generated LECT2-deficient (LECT2^<-/->) mice. We found that the proportion of natural killer T (NKT) cells in the liver increased significantly in LECT2^<-/-> mice, although those of conventional T cells, NK cells, and other cell types were comparable with those in wild-type mice. Consistent with increased hepatic NKT cell number, production of IL-4 and IFN-_Y was augmented in LECT2^<-/-> mice upon stimulation with α-galactosylceramide (α-GalCer), which specifically activates Vα14^+ NKT cells. In addition, NKT cell-mediated cytotoxic activity against syngeneic thymocytes also increased in hepatic mononuclear cells obtained from LECT2^<-/-> mice in vitro. Interestingly, the hepatic injury was exacerbated in LECT2^<-/-> mice upon treatment with Con A, possibly because of the significantly higher expression of IL-4 and Fas ligand. These results suggest that LECT2 might regulate the homeostasis of NKT cells in the liver, and might be involved in the pathogenesis of hepatitis.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] M, Ito, et al.: "Expression, oxidative refolding, and characterization of six-histidine-tagged recombinant human LECT2, a 16-kDa chemotactic protein with three disulfide bonds."Protein Expr Purif.. 27(2). 272-278 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M, Ito, et al.: "1H, 13C, 15N resonance assignments of the cytokine LECT2"Journal of Biomolecular NMR. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ovejero C., et al.: "Identification of the leukocyte cell-derived chemotaxin2 (LECT2) as a direct target gene of s-catenin in the liver"Hepatology. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito, T., et al.: "Increase of Hepatic NKT Cells in LECT2-Deficient Mice Contributes to Severe Concanavalin A-Induced Hepatitis"Journal of Immunology. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ito-ishida, M., Nagata, K., Oda, Y, Yamagoe, S., Suzuki, K., Tanokura, M.: "Expression, oxidative refolding and characterization of six-histidine-tagged recombinant human LECT2, a 16 kDa chemotactic protein with three disulfide bonds."Protein Expression Purif.. 27. 272-278 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ito, M., Nagata, N., Yumoto, F., Yamagoe, S., Suzuki, K., Adachi, K., Tanokura, M.: "1H,13C,15N resonance assignments of the cytokine LECT2."Journal of Biomolecular NMR. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ovejero C, Cavard C, Perianin A, Hakvoort T, Vermeulen J, Godard C, Fabre M, Chafey P, Suzuki K, Romagnolo B, Yamagoe S, Perret C.: "Identification of the leukocyte cell-derived chemotaxin2 (LECT2) as a direct target gene of s-catenin in the liver."Hepatology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito, T., Okumura, A., Watanabe, H., Asano, M., Ishida-Okawara, A., Sakagami, J., Sudo, K., Hatano-Yokoe, Y., Bezbradica, JS, Joyce, S., Abo, T., Iwakura, Y., Suzuki, K., Yamagoe S.: "Increase of Hepatic NKT Cells in LECT2-Deficient Mice Contributes to Severe Concanavalin A-Induced Hepatitis."Journal of Immunology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N, Sakai, et al.: "Involvement of histone acetylation in ovarian steroid-induced deciduali-Zation of human endometrial stromal cells."J.Biol.Chem. 278(19). 16675-16682 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohashi YY, et al.: "Novel missense mutation found in a Japanese patient with myeloperoxidase deficiency."Gene. 327(2). 195-200 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ovejero C, et al.: "Identification of the leukocyte cell-derived chemotaxin2(LECT2)as a direct target gene of s-catenin in the liver."Hepatology. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ito, M, et al.: "1H,13C,15N resonance assignments of the cytokine LECT2."Journal of Biomolecular NMR. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] S, Yamagoe, et al.: "Interaction of histone acetylases and deacetylases in vivo"Mol Cell Biol.. 23(3). 1025-1033 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] M, Ito, et al.: "Expression, oxidative refolding, and characterization of six-histidine-tagged recombinant human LECT2, a 16-kDa chemotactic protein with three disulfide bonds"Protein Expr Purif.. 27(2). 272-278 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] N, Sakai, et al.: "Involvement of histone acetylation in ovarian steroid-induced deciduali-Zation of human endometrial stromal cells"J. Biol. Chem.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Y, Murakami, et al.: "A mammanalian two-hybrid screening system for inhibitors of interaction between HIV Nef and the cellular tyrosine kinase Hck"Antiviral Research. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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