Benzo(a)pyrene inhibits growth and functional differentiation of mouse bone marrow-derived dendritic cells. Downregulation of RelB and eIF3 p170 by benzo(a)pyrene

• Published in: Toxicology letters Vol. 169; no. 1; p. 82
• Main Authors: Hwang, Ju-Ae, Lee, Jin-Ah, Cheong, Seon-Woo, Youn, Hyun-Joo, Park, Joo-Hung
• Format: Journal Article
• Language: English
• Published: Netherlands 28.02.2007
• Subjects: Animals; B7-2 Antigen - biosynthesis; Benzo(a)pyrene - toxicity; Bone Marrow Cells - drug effects; CD11c Antigen - biosynthesis; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cytokines - biosynthesis; Dendritic Cells - drug effects; Down-Regulation - drug effects; Eukaryotic Initiation Factor-3 - biosynthesis; Eukaryotic Initiation Factor-3 - genetics; Flow Cytometry; Genes, MHC Class II - drug effects; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Immunosuppressive Agents; Indicators and Reagents; Interleukin-4 - biosynthesis; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred BALB C; Polychlorinated Dibenzodioxins - toxicity; Receptors, Aryl Hydrocarbon - drug effects; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - isolation & purification; Teratogens - toxicity; Transcription Factor RelB - biosynthesis; Transcription Factor RelB - genetics
• ISSN: 0378-4274
• DOI: 10.1016/j.toxlet.2007.01.001

In this study, we have investigated effects of benzo(a)pyrene (BP) on growth and functional differentiation of mouse bone marrow (BM)-derived dendritic cells (DC). 1 microM BP dramatically inhibited growth of BM cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). Although little alterations in surface expression of CD11c, major histocompatibility complex (MHC II), and CD86 molecules characteristic of mature DC were induced by BP, production of cytokines including IL-12, IL-10, and TNF-alpha, and allogeneic T cell stimulating ability were severely impaired. Some of the effects of BP were dependent on arylhydrocarbon receptor (AhR), because alpha-naphthoflavone, an AhR antagonist, suppressed the effects of BP on IL-12 production and T cell stimulating ability, but not on DC proliferation. Expression of RelB, a transcription factor necessary for DC differentiation and function, and eIF3 p170, a subunit of eukaryotic translation initiation factor (eIF)3, was reduced upon BP treatment.