title: Cytokine-mediated suppression of cytochrome P450 1A1 in Hepa-1c1c7 cells by pokeweed mitogen.
abstract: This study investigated the effects of pokeweed mitogen (PWM) on the regulation of cytochrome P450 (P450) 1A1 expression in an in vitro model, using murine hepatoma cell line Hepa-1c1c7 and murine macrophage cell line RAW 264.7 cell cultures. PWM added directly to Hepa-1c1c7 cells had no effect on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced P450 1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity. However, TCDD-induced EROD activity and P450 1A1 mRNA levels were markedly suppressed when Hepa-1c1c7 cells were cultured with PWM-treated conditioned media from RAW 264.7 in a dose-dependent manner. Concomitant treatment with PWM and pentoxifylline, a TNFalpha synthesis inhibitor, to RAW 264.7 cells decreased the suppressive effects of PWM on TCDD-induced EROD activity. In PWM-exposed RAW 264.7 cell cultures, TNFalpha and IL-6 levels increased in a dose-dependent fashion. When antibodies to TNFalpha or/and IL-6 were added to PWM-treated conditioned media from RAW 264.7, the suppression of EROD activity was inhibited. These results suggested the suppression of P450 1A1 by PWM was mediated exclusively by TNFalpha and IL-6, released from macrophages.
authors: Department of Pharmacy and Research Center for Proteineous Materials, Chosun University, 375 Seosuk-dong, 501-759, Kwangju, South Korea. hgjeong@mail.chosun.ac.kr
authors: H G
authors: HG
authors: Jeong
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D020868:Gene Silencing / Q000187:drug effects; D015850:Interleukin-6 / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011043:Pokeweed Mitogens / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D015850:Interleukin-6; D011043:Pokeweed Mitogens; D014409:Tumor Necrosis Factor-alpha; D019363:Cytochrome P-450 CYP1A1