There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
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.