Background The glucocorticoid receptor (GR) is able to participate in regulation of transcription by a variety of mechanisms, one of which involves DNA binding and recruitment of regulatory cofactors. The best-studied forms of the receptor are the 777-amino-acid α and the 742-amino-acid β variants. The β isoform, which does not bind cortisol in human subjects, has been proposed to be a dominant-negative inhibitor of the transcriptional activation-competent GRα isoform. Objective GRα has roles in both transcriptional activation and repression. We wished to determine the influence of GRβ on genes that are normally transcriptionally repressed by glucocorticoids. We studied IL5 and IL13 , which both contribute to the asthmatic phenotype. Methods We used transient transfection systems and coimmunoprecipitation experiments to determine whether GRβ has repressive activity on the promoters of the human IL5 and IL13 genes. Results GRβ is able to act as a transcriptional repressor of cytokine genes and mediates its function through the recruitment of histone deacetylase complexes. Conclusion GRα and GRβ act in a similar manner on IL5 and IL13 promoters, serving to repress transcription. In this circumstance GRβ does not act as a dominant-negative inhibitor of GRα.
