Glucocorticoid-regulated gene expression in the immune system. Analysis of glucocorticoid-regulated transcripts from the mouse macrophage-like cell line P388D1.

To further elucidate the molecular mechanisms underlying glucocorticoid-mediated immune suppression, we have exploited cDNA cloning and subtractive screening methods to identify glucocorticoid-regulated transcripts in the mouse macrophage-like cell line, P388D1. Two of the three isolated glucocorticoid-regulated mRNA species corresponded to genes potentially important to immunoregulation: one glucocorticoid-suppressed mRNA species probably encoded the previously uncloned 3-hydroxy-3-methylglutaryl coenzyme A reductase, an enzyme that appears important for in vitro immune responses. The other mRNA species showed glucocorticoid-increased mRNA steady-state levels and was transcribed from an endogenous ecotropic type C retroviral locus. This transcript gives rise to a protein (transmembrane retroviral protein, formerly p15E), which, along with its feline and human homologs, has been implicated in immunosuppression caused by mouse, cat, and human retroviruses. Our results raise the possibility that the immunosuppressive activity of glucocorticoids might be mediated, in part, by regulating the expression of the above immunoregulatory proteins.