Monocyte-derived dendritic cells that capture dead tumor cells secrete IL-12 and TNF-a through IL-12/TNF-a/NF-?B autocrine loop.

Autor: Onishi, Hideya, Kuroki, Hideo, Matsumoto, Kotaro, Baba, Eishi, Sasaki, Nobuhiko, Kuga, Hirotaka, Tanaka, Masao, Katano, Mitsuo, Morisaki, Takashi
Předmět:
Zdroj: Cancer Immunology, Immunotherapy; Dec2004, Vol. 53 Issue 12, p1093-1100, 8p
Abstrakt: 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 a (TNF-a). Mo-DCs-Tum showed higher secretions of IL-12 and TNF-a than were shown by Mo-DCs. Enhanced nuclear factor-kappa B (NF-?B) activation was also induced in Mo-DCs-Tum within 6 h. The NF-?B inhibitor, pyrrolidine dithiocarbamate (PDTC), suppressed both IL-12 and TNF-a secretions from Mo-DCs-Tum. Administration of recombinant TNF-a or IL-12 enhanced IL-12 or TNF-a secretion respectively in Mo-DCs-Tum. Addition of anti-TNF-a or anti-IL-12 neutralizing antibody decreased NF-?B activation and IL-12 or TNF-a secretion in Mo-DCs-Tum. These results suggest that TNF-a or IL-12 secretion induces NF-?B activation, and it stimulates further TNF-a and IL-12 secretions, i.e., an IL-12/TNF-a/NF-?B autocrine loop, in Mo-DCs-Tum. Thus, Mo-DCs-Tum secrete a large amount of IL-12 and TNF-a through accelerated NF-?B activation induced by the IL-12/TNF-a/NF-?B autocrine loop. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index