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Productive role of fractalkine and CXCL16 in human epidermal keratinocytes

Research Project

Project/Area Number 16591103
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionEhime University

Principal Investigator

TOHYAMA Mikiko  Ehime University, University Hospital, Instructor, 医学部附属病院, 助手 (60263935)

Co-Investigator(Kenkyū-buntansha) SHIRAKATA Yuji  Ehime University, School of medicine, Lecturer, 医学部, 講師 (50226320)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsCXCL16 / fractalkine / chemokine / keratinocyte / toll-like receptor
Research Abstract

CXCL16 is a ligand for CXCR6, a CXC-chemokine receptor. CXCL16 is synthesized as a membrane-bound form that is cleaved to a soluble form that is a chemoattractant for CXCR6-expressing cells such as activated CD8 T cells, NKT cells, and Th1-polarized CD4 and CD8 T cells. By contrast, a membrane-bound form of CXCL16 expressed on human macrophages and dendritic cells acts as a scavenger receptor for oxidized low density lipoprotein. In addition, CXCL16 expressed on macrophages mediates adhesion and phagocytosis of bacteria such as Escheria coli or Staphylococcus aureus. The soluble chemokine domain of CXCL16 at concentrations > 5 □g/ml had antimicrobial activity against S.aureus and E.coli. Addition of 10 □g/ml soluble CXCL16 reduced the survival rate of S.aureus and E.coli by 70 and 40%, respectively. Because CXCL16 is produced constitutively by HEK, CXCL16 contributes to host-defense function in relation to microbial pathogens in human skin as well as □-defensins.
Fractalkine/CX3CL1, a chemokine, is synthesized as a membrane bound form and converted to a soluble form by protease(s). Since fractalkine recruits CX3CR1 positive cells such as NK cells and CD8+ T cells, it is supposed to be involved in recruiting these cells into the epidermis in the inflammatory reaction. To address this issue, we investigated whether normal human keratinocytes can produce fractalkine in the presence of cytokines. TNF-□, IL1-□□ and IFN-□ synergistically enhanced IFN-□-induced fractalkine production in normal human keratinocytes. In conclusion, this is the first report showing that normal human keratinocytes produce soluble fractalkine protein.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (24 results)

All 2006 2005 2004

All Journal Article (24 results)

  • [Journal Article] Bone morphogenetic protein-2 modulates Wnt and frizzled expression and enhances the canonical pathway of Wnt signaling in normal keratinocytes.2006

    • Author(s)
      Yang L, Yamasaki K, Shirakata Y, Dai x, Tokumaru S, Yahata Y, Tohyama M et al.
    • Journal Title

      The Journal of Dermatological Science In press

    • NAID

      10020549817

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SOCS1 negative feedback of STAT1 activation is a key pathway in the dsRNA-induced innate immune response of human keratinocytes.2006

    • Author(s)
      Dai X, Sayama K, Yamasaki K, Tohyama M, Shirakata Y et al.
    • Journal Title

      The Journal of Investigative Dermatology In press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bone morpholenetic protein-2 modulate Wnt signaling in normal keratinocytes.2006

    • Author(s)
      Yang L, Yamasaki K, Shirakata Y, et al.
    • Journal Title

      J Dermatol Sci (in Press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SOCS1 negative feedback of STATI activation is a key pathway in the dsRNA-induced innate immune response of human keratinocytes.2006

    • Author(s)
      Dai X, Sayama K, Yamasaki K, et al.
    • Journal Title

      J Invest Dermatol (in Press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bone morphogenetic protein-2 modulates Wnt and frizzled expression and enhances the canonical pathway of Wnt signaling in normal keratinocytes.2006

    • Author(s)
      Yang L, Yamasaki K, Shirakata Y, Dai X, Tokumaru S, Yahata Y, Tohyama M, et al.
    • Journal Title

      The Journal of Dermatological Science (In press)

    • NAID

      10020549817

    • Related Report
      2005 Annual Research Report
  • [Journal Article] SOCS1 negative feedback of STAT1 activation is a key pathway in the dsRNA-induced innate immune response of human keratinocytes.2006

    • Author(s)
      Dai X, Sayama K, Yamasaki K, Tohyama M, Shirakata Y, et al.
    • Journal Title

      The Journal of Investigative Dermatology (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] SOCS3/CIS3 negative regulation of STAT3 in HGF-induced keratinocyte migration.2005

    • Author(s)
      Tokumaru S, Sayama K, Yamasaki K et al.
    • Journal Title

      Biochem Biophys Res Commun. 327・1

      Pages: 100-105

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] dsRNA-mediated innate immunity of epidermal keratinocytes.2005

    • Author(s)
      Tohyama M, Dai X, Yamasaki K, Shirakata Y et al.
    • Journal Title

      Biochem Biophys Res Commun. 335

      Pages: 505-511

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Microbubble-enhanced ultrasound for gene transfer into living skin equivalents.2005

    • Author(s)
      Yang L, Shirakata Y, Tamai K, Dai X, Hanakawa Y, Tokumaru S, Yahata Y, Tohyama M et al.
    • Journal Title

      The Journal of Dermatological Science 40

      Pages: 105-114

    • NAID

      10018032379

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Induction of keratinocyte migration via transactivation of the EGF receptor by the antimicrobial peptide LL-37.2005

    • Author(s)
      Tokumaru S, Sayama K, Shirakata Y, Komatsuzawa H, Ouhara K, Hanakawa Y, Yahata Y, Dai x, Tohyama M et al.
    • Journal Title

      Journal of Immunology 175

      Pages: 4662-4668

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SOCS/CIS3 negative regulation of STAT3 in HGF-induced keratinocyte migration.2005

    • Author(s)
      Tokumaru S, Sayama K, Yamasaki K, et al.
    • Journal Title

      Biochem Biophys Res Commu 327-1

      Pages: 100-105

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DsRNA-mediated innate immunity of epidermal keratinocytes.2005

    • Author(s)
      Tohyama M, Dai X, Yamasaki K, et al.
    • Journal Title

      Biochem Biophys Res Commu 335

      Pages: 505-511

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Microbubble-enhanced ultrasound for gene transfer into living skin equivalents.2005

    • Author(s)
      Yang L, Shirakata Y, tamai K, et al.
    • Journal Title

      J Dermatol Sci 40

      Pages: 105-114

    • NAID

      10018032379

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Induction of keratinocyte migration via transactivation of the EGF receptor by the antimicrobial peptide LL-37.2005

    • Author(s)
      Tokumaru S, Sayama K, Shirakata Y, et al.
    • Journal Title

      J Immunol 175

      Pages: 4662-4668

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] dsRNA-mediated innate immunity of epidermal keratinocytes.2005

    • Author(s)
      Tohyama M, Dai X, Yamasaki K, Shirakata Y, et al.
    • Journal Title

      Biochem Biophys Res Commun. 335

      Pages: 505-511

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Microbubble-enhanced ultrasound for gene transfer into living skin equivalents.2005

    • Author(s)
      Yang L, Shirakata Y, Tamai K, Dai X, Hanakawa Y, Tokumaru S, Yahata Y, Tohyama M, et al.
    • Journal Title

      The Journal of Dermatological Science 40

      Pages: 105-114

    • NAID

      10018032379

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Induction of keratinocyte migration via transactivation of the EGF receptor by the antimicrobial peptide LL-37.2005

    • Author(s)
      Tokumaru S, Sayama K, Shirakata Y, Komatsuzawa H, Ouhara K, Hanakawa Y, Yahata Y, Dai X, Tohyama M, et al.
    • Journal Title

      Journal of Immunology 175

      Pages: 4662-4668

    • Related Report
      2005 Annual Research Report
  • [Journal Article] SOCS3/CIS3 negative regulation of STAT3 in HGF-induced keratinocyte migration.2005

    • Author(s)
      Tokumaru S, Sayama K, Yamasaki K, et al.
    • Journal Title

      Biochem Biophys Res Commun. 327・1

      Pages: 100-105

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transcriptional downregulation of DC-SIGN in human herpesvirus 6- infected dendritic cells.2004

    • Author(s)
      Niiya H, Azuma T, Jin L. et al.
    • Journal Title

      J Gen Virol 85・9

      Pages: 2639-2642

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] TGF-beta is not involved in early phase growth inhibition of keratinocytes by lalpha,25(OH)2vitamin D3.2004

    • Author(s)
      Shirakata Y, Ueno H, Hanakawa Y et al.
    • Journal Title

      J Dermatol Sci 36・1

      Pages: 41-50

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional down regulation of DC-SIGN in human herpesvirus 6-infected dendritic cells.2004

    • Author(s)
      Niiya H, Azuma T, Jin L, et al.
    • Journal Title

      J Gen Virol 85-9

      Pages: 2639-2642

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] TGF-bete is not involved in early phase growth inhibition of keratinocytes by 1 alpha, 25(OH)2 vitamin D3.2004

    • Author(s)
      Shirakata Y.Ueno H, Hanakawa Y, et al.
    • Journal Title

      J Dermatol Sci 36-1

      Pages: 41-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional downregulation of DC-SIGN in human herpesvirus 6-infected dendritic cells.2004

    • Author(s)
      Hiiya H, Azuma T, Jin L, et al.
    • Journal Title

      J Gen Virol 85・9

      Pages: 2639-2642

    • Related Report
      2004 Annual Research Report
  • [Journal Article] TGF-beta is not involved in early phase growth inhibition of keratinocytes by 1alpha,25(OH)2vitamin D3.2004

    • Author(s)
      Shirakata Y, Ueno H, Hanakawa Y, et al.
    • Journal Title

      J Dermatol Sci 36・1

      Pages: 41-50

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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