Monocyte-derived dendritic cells that capture dead tumor cells secrete IL-12 and TNF-alpha through IL-12/TNF-alpha/NF-kappaB 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-kappaB) activation was also induced in Mo-DCs-Tum within 6 h. The NF-kappaB 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-kappaB activation and IL-12 or TNF-alpha secretion in Mo-DCs-Tum. These results suggest that TNF-alpha or IL-12 secretion induces NF-kappaB activation, and it stimulates further TNF-alpha and IL-12 secretions, i.e., an IL-12/TNF-alpha/NF-kappaB autocrine loop, in Mo-DCs-Tum. Thus, Mo-DCs-Tum secrete a large amount of IL-12 and TNF-alpha through accelerated NF-kappaB activation induced by the IL-12/TNF-alpha/NF-kappaB autocrine loop.
Onishi
Hideya
H
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Kuroki
Hideo
H
Matsumoto
Kotaro
K
Baba
Eishi
E
Sasaki
Nobuhiko
N
Kuga
Hirotaka
H
Tanaka
Masao
M
Katano
Mitsuo
M
Morisaki
Takashi
T
D017209:Apoptosis; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology*; D016328:NF-kappa B / Q000502:physiology*; D009336:Necrosis; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C020972:pyrrolidine dithiocarbamic acid