Inhibition of Mineralocorticoid-Mediated Transcription by NF-κB

Nuclear factor-κB (NF-κB) is a ubiquitous transcription factor that regulates the expression of multiple inflammatory and immune response genes and plays a critical role in host defense and in chronic inflammatory diseases. The mineralocorticoid receptor (MR) belongs to the steroid/thyroid hormone receptor superfamily of ligand-induced transcription factors. We demonstrate a dose-dependent, mutual transcriptional antagonism between NF-κB and MR in transient transfection experiments. We also show that the antagonism is limited to the p65 subunit of NF-κB heterodimer but not p50. Transient cotransfection experiments with MR deletion constructs reveal the necessity of various N-terminal MR domains for this phenomenon. Inhibition of NF-κB by IκB relieves the repression of NF-κB function by MR. These data suggest that the p65 subunit of NF-κB interacts with MR indirectly and transrepresses MR activation.