| Project/Area Number |
14571674
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
KUMAGAI Naoki Yamaguchi University, School of Medicine, Assistant professor, 医学部, 助教授 (20234510)
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| 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)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| 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)
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| Keywords | corneal fibroblasts / LPS / IL-8 / MCP-1 / ICAM-1 / TLR-4 / CD14 / LBP |
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| 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
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