Regulation of IL 3 expression by glucocorticoids in cloned murine T lymphocytes

Abstract

We have examined the effects of glucocorticoids on the concanavalin A (Con A)-stimulated production of interleukin 3 (IL 3) by a murine helper T cell clone Cl.Ly-1+2-/9. The addition of Con A to Cl.Ly-1+2-/9 cells leads to the rapid induction of both IL 3 mRNA and activity. A synthetic glucocorticoid, dexamethasone, inhibits the appearance of IL 3 activity in the supernatants of Con A-stimulated cells, as well as the accumulation of IL 3 mRNA in the cells. A similar effect is observed with other Con A-inducible mRNA, such as the mRNA encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), but the hormone effects are not general; the constitutive synthesis of Thy-1 mRNA is not altered by dexamethasone treatment. Several lines of evidence suggest that dexamethasone directly inhibits transcription of the IL 3 gene: the kinetics of dexamethasone action on IL 3 mRNA are rapid; the stability of IL 3 mRNA is not affected by dexamethasone; hormone treatment does not inhibit either mRNA processing or transport from the nucleus. Our findings demonstrate that a set of mitogen-inducible genes in helper T cells can be subject to a second level of regulation mediated by glucocorticoid hormones.