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The Journal of Immunology, 1999, 163: 374-379.
Copyright © 1999 by The American Association of Immunologists

Estrogen Protects Against Cellular Infiltration by Reducing the Expressions of E-Selectin and IL-6 in Endotoxin-Induced Uveitis1

Noriko Miyamoto, Michiko Mandai2, Izumi Suzuma, Kiyoshi Suzuma, Kaori Kobayashi and Yoshihito Honda

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan

Anterior uveitis associated with Behcet’s disease and ankylosing spondylitis preferentially occurs in adult men, which may suggest the effects of sex hormones on acute anterior uveitis. Recently, estrogen receptors in the vascular endothelium have been reported to be involved in several pathological conditions. In the present study, we examined the gender differences in susceptibility to endotoxin-induced uveitis (EIU) and the effects of estrogen on anterior inflammation. EIU was induced in adult male, female, and ovariectomized female Lewis rats (200 g) by hind footpad injection of 200 µg of LPS. In EIU, cellular infiltration was more marked in male than in female rats, and ovariectomy increased cellular infiltration. Treatment with 10 µg of 17ß-estradiol significantly reduced the cell number in male and ovariectomized female rats with EIU. Estrogen receptor immunoreactivity was found in the nucleus of vascular endothelium and in some stromal cells of the iris-ciliary body. Semiquantitative PCR revealed that E-selectin and IL-6 gene expressions were increased in rats following LPS injection, and an overdose of tamoxifen, an estrogen receptor antagonist, reversed the effect of 17ß-estradiol on E-selectin, but not its effect on IL-6. These observations suggested that the down-modulation of these inflammatory genes by estrogen may contribute to the reduction in cellular infiltration in acute anterior uveitis.




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