RT Journal Article
SR Electronic
T1 IL-1 beta modulates the concanavalin-A-induced expression of proenkephalin A mRNA in murine thymocytes.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1566
OP 1572
VO 267
IS 3
A1 K M Linner
A1 S E Nicol
A1 B M Sharp
YR 1993
UL http://jpet.aspetjournals.org/content/267/3/1566.abstract
AB 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-1 beta (mIL-1 beta) in a biphasic, dose-dependent manner. Murine thymocytes were cultured for 72 h with Con-A and with varying concentrations of mIL-1 beta. PEA mRNA expression was analyzed by Northern gel and solution hybridization techniques. Concentrations of mIL-1 beta 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-1 beta (10(-11) and 10(-10) M) inhibited its expression 60 and 85%, respectively. Both the enhancing and inhibiting effects of mIL-1 beta 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-1 beta 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 [3H]thymidine incorporation. The present study demonstrates that PEA mRNA expression is regulated by IL-1 beta, which is thought to play a role in thymocyte maturation.