Suppression of Cytokine-induced Expression of Endothelin-1 by Dexamethasone in Human Retinal Pigment Epithelial Cells

Abstract

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-gamma, tumor necrosis factor-alpha and interleukin-1beta, 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.