2,3,7,8-Tetrachlorodibenzo-p-dioxin modulates functional differentiation of mouse bone marrow-derived dendritic cells Downregulation of RelB by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
We have previously shown that benzo(a)pyrene inhibits the growth and functional differentiation of mouse bone marrow (BM)-derived dendritic cells (DCs) [Hwang, J.A., Lee, J.A., Cheong, S.W., Youn, H.J., Park, J.H., 2007. 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. Toxicol. Lett. 169, 82-90]. Since the toxic effects of benzo(a)pyrene are aryl hydrocarbon receptor (AhR)-dependent, we examined the effects of the very potent AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the growth and functional differentiation of mouse BM-derived DCs. Ten nanomolars of TCDD had significant effects on functional differentiation of mouse DCs derived from BM cultured in the presence of GM-CSF and IL-4. The yields of DCs, flow-cytometrically analyzed for co-expression of CD11c/MHCII or CD11c/CD86, were reduced for TCDD-treated cultures, but TCDD itself had no effect on the growth of BM. DCs from TCDD-treated cultures expressed higher levels of MHCII and CD86, whereas expression of CD11c was reduced, compared with vehicle-treated cultures. Production of IL-10, but not IL-12, by the DCs from TCDD-treated cultures was decreased. Allogeneic T-cell stimulating ability of TCDD-treated DCs was increased compared to control DCs. The effects of TCDD were dependent on aryl hydrocarbon receptor (AhR), because alpha-naphthoflavone, an AhR antagonist, suppressed the effects of TCDD on IL-10 production and T-cell stimulating ability. RT-PCR revealed the downregulation of RelB, a transcription factor necessary for DCs differentiation and function. Taken together, although benzo(a)pyrene and TCDD exert their effects via binding to AhR, their effects on the growth and functional differentiation of bone marrow-derived DCs are different.
Department of Biology, Changwon National University, #9 Sarim-dong, Changwon, Kyungnam 641-773, South Korea.
Jin-Ah
JA
Lee
Ju-Ae
JA
Hwang
Ha-Na
HN
Sung
Chang-Hwan
CH
Jeon
Byoung-Chul
BC
Gill
Hyun-Joo
HJ
Youn
Joo-Hung
JH
Park
D000818:Animals; D051940:B7-2 Antigen / Q000096:biosynthesis; D051792:Basic Helix-Loop-Helix Proteins; D001571:Benzoflavones / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D039521:CD11c Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D004785:Environmental Pollutants / Q000633:toxicity*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects; D051841:Transcription Factor RelB / Q000235:genetics / Q000378:metabolism*
D051940:B7-2 Antigen; D051792:Basic Helix-Loop-Helix Proteins; D001571:Benzoflavones; D039521:CD11c Antigen; D004785:Environmental Pollutants; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D051841:Transcription Factor RelB; C484722:Ahr protein, mouse; C497965:Cd86 protein, mouse; C497594:Relb protein, mouse; C011512:alpha-naphthoflavone