IL-1-BETA MODULATES THE CONCANAVALIN-A-INDUCED EXPRESSION OF PROENKEPHALIN-A MESSENGER-RNA IN MURINE THYMOCYTES

We have previously shown that proenkephalin A (PEA) messenger RNA (mRNA) is induced in murine thymocytes by the T cell-specific mitogen concanavalin-A (Con-A). We now show that this Con-A-induced expression of PEA mRNA is modulated by the cytokine murine interleukin-1beta (mIL-1beta) in a biphasic, dose-dependent manner. Murine thymocytes were cultured for 72 h with Con-A and with varying concentrations of mIL-1beta. PEA mRNA expression was analyzed by Northern gel and solution hybridization techniques. Concentrations of mIL-1beta of 10(-14) and 10(-13) M enhanced the Con-A-induced expression of PEA mRNA in cultured murine thymocytes up to 2.5-fold, whereas higher concentrations of mIL-1beta (10(-11) and 10(-10) M) inhibited its expression 60 and 85%, respectively. Both the enhancing and inhibiting effects of m[L-1beta in the Con-A-induced expression of PEA mRNA were reversed by a 100-fold excess of interleukin-1 receptor antagonist protein, but not by a 10-fold excess of interleukin-1 receptor antagonist protein. The effects of mIL-1beta on PEA mRNA expression in Con-A-activated thymocytes are different from its effects on Con-A-stimulated thymocyte proliferation. In the latter case, only enhancement of thymocyte proliferation was seen, as measured by [H-3]thymidine incorporation. The present study demonstrates that PEA mRNA expression is regulated by IL-1beta which is thought to play a role in thymocyte maturation.