Inhibition by (±)-indenestrol A of interferon gamma-stimulated nitric oxide formation in murine macrophage RAW 264.7 cells

Taiko Oda, You So, Yoshihiro Sato, Noriaki Shimizu, Hiroshi Handa, Yukio Yasukochi, Tadashi Kasahara

研究成果: Article査読

4 被引用数 (Scopus)

抄録

We examined the effects of (±)-indenestrol A (IA), an antioxidative and superoxide-producing metabolite of diethylstilbestrol (DES), on the activation of murine macrophages (RAW 264.7 cells) in vitro, particularly with regard to interferon (IFN)-γ-induced nitric oxide (NO) production. (±)-IA inhibited NO production more strongly than DES as assessed by a nitrite assay. The inhibitory effect of (±)-IA on IFN-γ-induced intracellular NO production was confirmed by direct staining of intracellular NO with diaminofluorescein-2 diacetyl. Inhibition of NO production was confirmed by Western blot analysis of IFN-γ-induced NO synthase. Under IFN-γ-stimulated conditions, the IFN-γ activation site (GAS), which was the most important transcription factor, was significantly inhibited by (±)-IA. (±)-IA also promoted the activation of NF-κB. (±)-IA at 1 and 3μM delayed the onset of apoptosis. Our results suggest that (±)-IA inhibited the activation of macrophages, resulting in the suppression of NO-mediated apoptosis. These results suggest a novel mechanism for the carcinogenic promoting activity of DES via its metabolite, (±)-IA.

本文言語English
ページ(範囲)187-195
ページ数9
ジャーナルMutation Research - Genetic Toxicology and Environmental Mutagenesis
534
1-2
DOI
出版ステータスPublished - 2003 1月 10

ASJC Scopus subject areas

  • 遺伝学
  • 健康、毒物学および変異誘発

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