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Research on the innate immune system of the cornea

Research Project

Project/Area Number 14571674
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionYamaguchi University

Principal Investigator

KUMAGAI Naoki  Yamaguchi University, School of Medicine, Assistant professor, 医学部, 助教授 (20234510)

Co-Investigator(Kenkyū-buntansha) FUKUDA Ken  Yamaguchi University, School of Medicine, Research Associate, 医学部, 寄附講座教員 (70335751)
SEKI Keisuke  Yamaguchi University, School of Medicine, Assistant Professor, 医学部, 客員助教授 (50318820)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordscorneal fibroblasts / LPS / IL-8 / MCP-1 / ICAM-1 / TLR-4 / CD14 / LBP
Research Abstract

In order to clarify the roles of corneal cells in innate immune system of the cornea, we revealed the following facts
1) Cultured human corneal fibroblasts express toll-like receptor (TLR)-4 and cluster of differentiation (CD) 14, which are the components of LPS receptors. These cells also express MD-2 protein, which is necessary for the proper distribution of LPS receptors on the cell membrane
2) LPS derived from E Coli, P.aerubginosa and S Minnesota enhanced the expression of IL-8, MCP-1 and ICAM-1 by cultured human corneal fibroblast. This effect was time and dose-dependent. The effect of LPS on the expression on these proteins are E.coli> S.Minnesota>> P.aeruglnosa
3) Human tear fluids did contain LBP and sCD14. The concentrations of these LPS-related proteins were about 1 micro gram 1 ml and 400 nano gram /ml, respectively. The concentrations of these LPS-related proteins were lower in the tear fluids than that in the serum measured with a same settings. There were no relationships b … More etween the concentration of these LPS-related proteins in the tear fluids and the serum
4) Addition of LBP or sCD14 induced a dose dependent increase of IL-8 release and ICAM-1 expression by cultured human corneal fibroblasts. The stimulatory effect of these LPS-related proteins axe more pronounced at a concentration of the serum than that of the tear fluids
5) Injection of LPS into a rabbit corneal stroma induced a corneal ulcer and corneal opacity. These corneal lesions are transient the cornea is healed spontaneously leaving corneal scarring. Histologically, infiltration of neutrophils is observed in to the corneal stroma
Our study shows that the cells of the cornea, especially the corneal fibroblasts, play a role in the innate immune system of the outer eye. These cells perceive the presence of LPS, which is a common structure of Gram negative bacterial cell walls, and express neutrophils activation and chemotactic factors such as ICAM-1 and IL-8
LPS-related proteins such as LBP or sCD14 enhance the perception of LPS by corneal cells Less

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Naoki Kumagai et al.: "Active matrix metalloproteinases in the tear fluid of individuals with vernal keratoconjunctivitis"The Journal of Allergy and Clinical Immunology. 110. 489-491 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ken Fukuda et al.: "Inhibition of eotaxin expression in human corneal fibroblasts by interferon-γ"International Archives of Allergy and Immunology. 129. 138-144 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Youichiro Fujitsu et al.: "IL-4-induced cell proliferation and production of extracellular matrix proteins in human conjunctival fibroblasts"Experimental Eye Research. 76. 107-114 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ken Fukuda et al.: "Differential expression of thymus- and activation-regulated chemokine(CCL17) and macrophage-derived chemokine(CCL22) by human fibroblasts from cornea, skin, and lung"The Journal of Allergy and Clinical Immunology. 111. 520-526 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Naoki Kumagai et al.: "Expression of functional ICAM-1 on cultured human keratocytes induced by tumor necrosis factor-α"Japanese Journal of Ophthalmology. 47. 134-141 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Naoki Kumagai et al.: "Synergistic effect of TNF-α and either IL-4 or IL-13 on VCAM-1 expression by cultured human corneal fibroblasts"Cornea. 22. 557-561 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Qin Li et al.: "Enhancement by neutrophils of collagen degradation by corneal fibroblasts"Journal of Leukocyte Biology. 74. 412-419 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ying Lu et al.: "Inhibition by triptolide of IL-1-induced collagen degradation by corneal fibroblasts"Investigative Ophthalmology and Visual Science. 44. 5082-5088 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Naoki Kumagai et al.: "Active matrix metalloproteinases in the tear fluid of individuals with vernal keratoconjunctivitis"The Journal of Allergy and Clinical Immunology. 110-3. 489-491 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ken Fukuda et al.: "Inhibition of eotaxin expression in human corneal fibroblasts by interferon-y"International Archives of Allergy and Immunology. 129-2. 138-144 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Youichiro Fujitsu et al.: "IL-4-induced cell proliferation and production of extracellular matrix proteins in human conjunctival fibroblasts"Experimental Eye Research. 76-1. 107-114 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ken Fukuda et al.: "Differential expression of thymus and activation-regulated chemokine (CCL17) and macrophage-derived chemokine (CCL22) by human fibroblasts from cornea, skin, and lung"The Journal of Allergy and Clinical Immunology. 111-3. 520-526 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Naoki Kumagai et al.: "Expression of functional ICAM-1 on cultured human keratocytes induced by tumor necrosis factor-a"Japanese Journal of Ophthalmology. 47-2. 134-141 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Naoki Kumagai et al.: "Synergistic effect of TNF-a and either IL-4 or IL-13 on VCAM-1 expression by cultured human corneal fibroblasts"Cornea. 22-6. 557-561 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Qin Li et al.: "Enhancement by neutrophils of collagen degradation by corneal fibroblasts"Journal of Leukocyte Biology. 74-3. 412-419 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ying Lu et al.: "Inhibition by triptolide of IL-1-induced collagen degradation by corneal fibroblasts"Investigative Ophthalmology and Visual Science. 44-12. 5082-5088 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ken Fukuda et al.: "Differential expression of thymus- and activation-regulated chemokine(CCL17) and macrophage-derived chemokine(CCL22) by human fibroblasts from cornea, skin, and lung"The Journal of Allergy and Clinical Immunology. 111・3. 520-526 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Naoki Kumagai et al.: "Expression of functional ICAm-1 on cultured human keratocytes induced by tumor necrosis factor-α"Japanese Journal of Ophthalmology. 47・2. 134-141 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Naoki Kumagai et al.: "Synergistic effect of TNF-α and either IL-4 or IL-13 on VCAM-1 expression by cultured human corneal fibroblasts"Cornea. 22・6. 557-561 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Qin Li et al.: "Enhancement by neutrophils of collagen degradation by corneal fibroblasts"Journal of Leukocyte Biology. 74・3. 412-419 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ying Lu et al.: "Inhibition by triptolide of IL-1-Induced collagen degradation by corneal fibroblasts"Investigative Ophthalmology and Visual Science. 44・12. 5082-5088 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Naoki Kumagai et al.: "Active matrix metalloproteinases in the tear fluid of individuals with vernal keratoconjunctivitis"THE Journal of Allergy and Clinical Immunology. 110・3. 489-491 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ken Fukuda et al.: "Inhibition of eotaxin expression in human corneal fibroblasts by interferon-γ"International Archives of Allergy and Immunology. 129・2. 138-144 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Youichiro Fujitsu et al.: "IL-4-induced cell proliferation and production of extracellular matrix proteins in human conjunctival fibroblasts"Experimental Eye Research. 76・1. 107-114 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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