Monocyte-derived dendritic cells that capture dead tumor cells secrete IL-12 and TNF-α through IL-12/TNF-α/NF-κB autocrine loop

This study focused on the question of how monocyte-derived dendritic cells (Mo-DCs) that capture dead tumor cells (Mo-DCs-Tum) secrete interleukin 12 (IL-12) and tumor necrosis factor alpha (TNF- alpha ). Mo-DCs-Tum showed higher secretions of IL-12 and TNF- alpha than were shown by Mo-DCs. Enhanced nuclear factor-kappa B (NF- Kappa B) activation was also induced in Mo-DCs-Tum within 6 h. The NF- Kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC), suppressed both IL-12 and TNF- alpha secretions from Mo-DCs-Tum. Administration of recombinant TNF- alpha or IL-12 enhanced IL-12 or TNF- alpha secretion respectively in Mo-DCs-Tum. Addition of anti-TNF- alpha or anti-IL-12 neutralizing antibody decreased NF- Kappa B activation and IL-12 or TNF- alpha secretion in Mo-DCs-Tum. These results suggest that TNF- alpha or IL-12 secretion induces NF- Kappa B activation, and it stimulates further TNF- alpha and IL-12 secretions, i.e., an IL-12/TNF- alpha /NF- Kappa B autocrine loop, in Mo-DCs-Tum. Thus, Mo-DCs-Tum secrete a large amount of IL-12 and TNF- alpha through accelerated NF- Kappa B activation induced by the IL-12/TNF- alpha /NF- Kappa B autocrine loop.