Calcium mediates one of the signals required for interleukin 1 and 2 production by murine cell lines

Abstract

The murine T lymphoma cell line EL-4 can be induced to produce interleukin 2 (IL-2) by concurrent stimulation with interleukin 1 (IL-1) and a T-cell lectin such as phytohemagglutinin (PHA) or concanavalin A (Con A). The results presented here demonstrate that the requirement for the lectin, but not IL-1, could be completely replaced by the calcium ionophore A23187. The optimal effective concentration of A23187 was found to be 2.5 X 10(-7) M, and the costimulating effect of IL-1 was dose-dependent. The stimulatory effect of A23187 was completely eliminated by incorporation of 5 mM ethylene glycol bis (beta-aminoethyl ether) N,N,N',N'-tetracetic acid (EGTA) in the culture medium, and this inhibition could in turn be reversed by addition of 5 mM CaCl2 to the medium. Release of IL-2 from IL-1/A23187-stimulated EL-4 was detected within 5 hr after initiation of the cultures, and both signals were required at the same time to initiate synthesis or release of IL-2. In addition, the calcium ionophore also augmented release of IL-1 from the P388D1 murine macrophage cell line. These results suggest that a calcium-mediated event may serve as a common mechanism for the induction of secretion of lymphokines and monokines from murine cell lines.