Calcium mobilizing treatment acts as a co-signal for TLR-mediated induction of Interleukin-12 (IL-12p70) secretion by murine bone marrow-derived dendritic cells.

We sought to determine whether pharmacological calcium-mobilizing agents could act in cooperation with Toll-like receptor (TLR) signals to induce high-level IL-12 production from murine bone marrow-derived dendritic cells. We found that calcium mobilization alone induced no IL-12, yet dramatically enhanced IL-12p70 secretion elicited by TLR ligands. Enhanced IL-12 production induced by calcium ionophore plus single TLR ligands, but not through dual TLR ligands, was inhibited by the calcineurin antagonist cyclosporine A, suggesting divergent mechanisms of IL-12 induction. Dendritic cells activated with calciumionophore plus the TLR9 ligand ODN1826 could induce Th1 polarization in naïve murine CD4pos T cells at levels equal or superior to dendritic cells activated with the most efficient TLR ligand pairing; ODN1826 plus bacterial lipopolysaccharide. Parallel analysis of 38 inflammation-associated soluble products showed calciumionophore enhancement was restricted to a small set of factors. These data demonstrate previously undocumented activation co-signals for IL-12 production by dendritic cells.