| Project/Area Number |
06671777
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Ophthalmology
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| Research Institution | Nihon University |
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Principal Investigator |
IWATA Mitsuhiro Nihon University Sch of Med, Ophthalmology, assistant, 医学部, 助手 (50193751)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Yoshihiro Nihon University Sch of Med, Immunobiochemistry, assistant, 医学部, 助手 (80206549)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Major histocompatibility complex / Intercelular adhesion molecule-1 / Interferon-gamma / Tumor necrosis factor-alpha / Tyrosine phosphorylation / Signal transduction / Mujor histocompatibity Complex / Intercellular adhesion molecule-1 / Interferon-galnlnd / Tumcr necrus fuctcr-alpha / Tyrosin phosphorylation / major histocompatibility complex / intercellular adhesion molecude-1 / interferon-gamma / tumor necrosisfactor-alpha / tyrosine kinase |
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| Research Abstract |
Mechanisms of signal transduction for regulatory effects of IFN-gamma and TNF-alpha on MHC molecules or ICAM-1 expression on human corneal epithelial (HCE) cells were examined by flow cytometry, Western blotting, and immunoprecipitation, using cultured HCE cells.
(1) Multiple strong tyrosine phosphorylation bands were detected in the IFN-gamma-treated HCE cells.
(2) Pretreatment of HCE cells I and class with herbimycin A (HMA), a specific protein kinase (PTK) inhibitor, blocked the IFN-gamma induction of both MHC class II expression.
(3) HMA had only a partial blocking effect on the IFN-gamma induction of ICAM-1 expression.
(4) HMA inhibited the protein tyrosine phosphorylation in the HCE cells induced by IFN-gamma.
(5) Both Jak1 and Jak2 molecules were detected in HCE cells.
<short conclusion> These results suggested that IFN-gamma induces tyrosine phosphorylation of proteins which may mediate the IFN-gamma induction of MHC class I and class II expression on HCE cells, but mediate the IFN-gamma induction of ICAM-1 partially.
(6) TNF-induced tyrosine phosphorylation of proteins which were similar but different from those by IFN-gamma in the HCE cells.
(7) Inhibitory effect of TNF-alpha on IFN-gamma induction of MHC class II on HCE cells was blocked by HMA.
<short conclusion> These findings suggested that TNF-alpha induces protein tyrosine phosphorylation which may mediate an inhibitory effect of TNF-alpha on the IFN-gamma -induction of MHC class II expression on HCE cells.
2.Interactions between human corneal stromal (HCF) cells and HCE cells were examined.
HCE cells cocultured with HCF cells expressed B7-1 molecules when stimulated by IFN-gamma, whereas HCE cells cultured alone did not express B7-1.
This finding suggested that immunological function of HCE cells is enhanced by HCF through B7-1 induction on HCE cells.
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