Suppression of cytokine-induced expression of endothelin-1 by dexamethasone in human retinal pigment epithelial cells

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-I mRNA expression levels and immunoreactive endothelin levels in the medium. These findings raise the possibility that anti-inflammatory effects of dexamethasone in eyes may be partly mediated or modulated by its effects on expression of ET-1.