title: Monocyte-derived dendritic cells that capture dead tumor cells secrete IL-12 and TNF-alpha through IL-12/TNF-alpha/NF-kappaB autocrine loop.
abstract: 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.
authors.affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Onishi
authors.forename: Hideo
authors.initials: H
authors.lastname: Kuroki
authors.forename: Kotaro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Eishi
authors.initials: E
authors.lastname: Baba
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Sasaki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kuga
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
authors.forename: Takashi
authors.initials: T
authors.lastname: Morisaki
mesh_terms: 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*
chemical_list: D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C020972:pyrrolidine dithiocarbamic acid