Competition for p300 Regulates Transcription by Estrogen Receptors and Nuclear Factor-κB in Human Coronary Smooth Muscle Cells

Abstract

—Previous studies suggest that estrogen may prevent expression of cell adhesion molecules implicated in vascular inflammation associated with atherosclerosis. We demonstrate the interaction and reciprocal interference of estrogen receptors (ERs) with p65, the nuclear factor-κB component, in smooth muscle cells that express ERα and ERβ after exposure to 17β-estradiol for 48 to 72 hours. ER and p65 do not associate directly, as shown by lack of coprecipitation, but instead compete for limiting amounts of p300, a close relative of the CREB-binding protein. Overexpressed p300 significantly reduced the inhibitory effect of ER on p65-dependent transcription as well as the inhibitory effect of p65 on ER-dependent transcription. These actions were ligand-dependent. The expression of both ER and nuclear factor-κB–dependent reporter genes was partially rescued from ER/p65 mutual inhibition by transient transfection of smooth muscle cells with a p300 expression vector. These actions of 17β-estradiol may play an important role in the cytokine-induced expression of immune and inflammatory genes implicated in atherogenesis.