1998 Fiscal Year Final Research Report Summary
Key Molecules involved in the Early Phase of Anterior Uveitis
| Project/Area Number |
09671793
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
MANDAI Michiko Kyoto University Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (80263086)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAGI Hitoshi Kyoto University Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (70283596)
KASHII Satoshi Kyoto University Graduate School of Medicine, Lecturer, 医学研究科, 講師 (50194717)
TANIHARA Hidenobu Kyoto University Graduate School of Medicine, Lecturer, 医学研究科, 講師 (60217148)
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| Project Period (FY) |
1997 – 1998
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| Keywords | LPS / cellular infiltration / endotoxin-induced uveitis / E-selectin / P-selectin / estrpgen / gene expression / vaxcular endothelium |
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| Research Abstract |
Endotoxin-induced uveitis (EIU) is an animal model of acute ocular inflammation caused by the injection of lipopolysaccharide (LPS). Selectins area group of molecules involved in rolling of leukocytes, the initial step of cellular infiltration. Among them, P-selectin is stored in the vascular endothelial cell body and translocated to the surface upon stimulation, whereas E-selectin is regulated at the transcriptional level of the gene. In EIU, we found that P-selectin appeared immunohistochemically on the endothelial surface of the vessels of iris-ciliary body after 15 minutes of LPS treatment, followed by its second expression at 3-5 hours after LPS injection, and that E-selectin appeared 7-24 hours after LPS treatment. Each of the neutralizing antibodies against P- and E-selectin similarly reduced the cellular infiltration in EIU, but anti P-selectin antibody given at 6 hours after LPS treatment did not significantly inhibit the cellular infiltration whereas anti E-selectin antibody
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given at any time after LPS treatment significantly reduced cellular infiltration thereafter. Semi-quantitative PCR revealed that E-selectin gene expression reached a peak at 6 hours after LPS treatment both in the iris-ciliary body and retina, and it returned to the basal level at the time of maximum uveitis. Simultaneous injection of anti P-and E-selectin antibodies almost abrogated cellular infiltration. These suggested that P-selectin is involved in the initiation of cellular infiltration whereas E-selectin contributes to retain cellular infiltration ; the inhibition of the former may contribute to the prevention of inflammation and the latter, to the early resolution of the inflammation. Next we focused on the fact that anterior uveitis associated with massive cellular infiltration is more often observed in men than in women, and we are studying the role of estrogen against cellular infiltration in EIU.Estrogen receptor-like immunoreactivity was found on the vascular endothelium of iris-ciliary body, and the degree of cellular infiltration was in the order of male>ovariectomized female>female rats. Intraperitoneal injection of estradiol significantly reduced cellular infiltration and the E-selectin gene expression, indicating that estrogen protects against cellular infiltration by modulation the selectin expression. Less
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