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.
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.
Hwang
Ju-Ae
JA
Department of Biology, Changwon National University, Changwon, Kyungnam 641-773, South Korea.
Lee
Jin-Ah
JA
Cheong
Seon-Woo
SW
Youn
Hyun-Joo
HJ
Park
Joo-Hung
JH
D000818:Animals; D051940:B7-2 Antigen / Q000096:biosynthesis; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects*; D039521:CD11c Antigen / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D039621:Eukaryotic Initiation Factor-3 / Q000096:biosynthesis* / Q000235:genetics; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; D015847:Interleukin-4 / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013723:Teratogens / Q000633:toxicity; D051841:Transcription Factor RelB / Q000096:biosynthesis* / Q000235:genetics
D051940:B7-2 Antigen; D039521:CD11c Antigen; D016207:Cytokines; D039621:Eukaryotic Initiation Factor-3; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C497594:Relb protein, mouse; D013723:Teratogens; D051841:Transcription Factor RelB; D015847:Interleukin-4; D001564:Benzo(a)pyrene; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor