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Udono-Fujimori Reiko; Totsune, Kazuhito; Murakami, Osamu; Arihara, Zenei; Kikuchi, Kumi; Tamai, Makoto; Shibahara, Shigeki; Takahashi, Kazuhiro
Journal of Cardiovascular Pharmacology: November 2004
doi: 10.1097/01.fjc.0000166311.53506.dd
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We have recently shown that retinal pigment epithelial cells secrete endothelin-1 (ET-1). In the present study, we studied effects of cytokines and dexamethasone on expression of ET-1 in two types of cultured human retinal pigment epithelial cells, ARPE- 19 cells and D407 cells. Treatment for 24 hours with a combination of three cytokines, interferon-γ, tumor necrosis factor- and interleukin-1β, induced expression of ET-1 in both cells. When treated with dexamethasone (10−7 mol/L) alone, the immunoreactive endothelin level in the medium increased about three-fold in D407 cells, but not in ARPE-19 cells. Dexamethasone (10−7 mol/L), however, suppressed the cytokine-mediated increases in ET-1 mRNA expression levels and immunoreactive endothelin levels in the medium. These findings raise the possibility that antiinflammatory effects of dexamethasone in eyes may be partly mediated or modulated by its effects on expression of ET-1.

Address correspondence and reprint requests to Dr Kazuhiro Takahashi, Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan. E-mail:

This work was supported in part by Grants-in-aid for Scientific Research (B) (Number 13470030) and (C) (Number 13671094) from the Ministry of Education, Science, Sports and Culture of Japan, by a Research Grant from the HIROMI Medical Research Foundation (2001) and by a Research Grant from the Intelligent Cosmos (2002).

© 2004 Lippincott Williams & Wilkins, Inc.