THE EFFECT OF CALCIUM MOBILIZATION ON LPS-INDUCED IL-1-BETA PRODUCTION DEPENDS ON THE DIFFERENTIATION STAGE OF THE MONOCYTES MACROPHAGES

The role of elevated intracellular calcium concentration [Ca2+]i in the LPS-induced activation of interleukin-1-beta (IL-1-beta) production was examined in cells representing different stages of myeloid differentiation (undifferentiated monocytic leukaemia cell line THP-1, THP-1 cells induced to adherent, macrophage-like cells by phorbol ester treatment and normal peripheral blood-derived adherent monocytes). LPS did not elevate the [Ca2+]i as measured by the Fura-2 fluorescence technique. When these cells were stimulated with LPS in the presence of the calcium ionophore A23187, a clear increase in the IL-1-beta protein production was observed in the undifferentiated THP-1 cells but not in the more differentiated cell types. This ionophore-induced increase was also seen in the IL-1-beta mRNA levels. Thus these data confirm the previous findings demonstrating that elevation of [Ca2+]i is not involved in the LPS-dependent signal transmission. However, the LPS-induced signals are greatly potentiated by the elevated [Ca2+]i, but only in undifferentiated monocytic cells.