IL-1 beta modulates the concanavalin-A-induced expression of proenkephalin A mRNA 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-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.
Linner
K M
KM
Endocrine-Neuroscience Research Laboratory, Minneapolis Medical Research Foundation, Minnesota.
Nicol
S E
SE
Sharp
B M
BM
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D003208:Concanavalin A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004745:Enkephalins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012795:Sialoglycoproteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D004745:Enkephalins; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011498:Protein Precursors; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C029992:proenkephalin; D003208:Concanavalin A