Differences in binding of glucocorticoid receptor to DNA in chronic renal graft rejection

Although chronic rejection is the most common reason for late allograft los s, its pathophysiology and etiology are unclear. Attempts to prevent chroni c rejection are now focused on the modulation of transcriptional regulation . We evaluated the ability of glucocorticold receptors (GR) to bind to the DNA binding site in peripheral blood mononuclear cells (PBMC) of five patie nts with chronic rejection and seven without it. Using an electrophoretic m obility shift assay, we measured the amount of nuclear glucocorticoid recep tor capable of binding to its specific DNA recognition sequences, termed gl ucocorticold response elements (GRE). GR binding was significantly greater in control patients than in those with chronic rejection (P < 0.01). The re tarded band was almost undetectable in two patients with chronic rejection even though they were taking more prednisolone than the seven control patie nts, all of whom had clearly identifiable retarded bands. These results sug gest a decreased ability of GR to bind to GRE in chronic rejection, resulti ng in a reduced ability to block key proinflammatory promoter sites. This r educed binding may be one molecular basis of chronic rejection.