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

Research output: Contribution to journalArticle

Abstract

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)-gamma-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-gamma-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-gamma-induced NO synthase. Under IFN-gamma-stimulated conditions, the IFN-gamma activation site (GAS), which was the most important transcription factor, was significantly inhibited by (+/-)-IA. (+/-)-IA also promoted the activation of NF-kappaB. (+/-)-IA at 1 and 3 microM 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.

Original languageEnglish
Pages (from-to)187-195
Number of pages9
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume534
Issue number1-2
Publication statusPublished - 2003 Jan 10

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Interferon-gamma
Nitric Oxide
Macrophages
Diethylstilbestrol
Macrophage Activation
Apoptosis
Diacetyl
RAW 264.7 Cells
indenestrol
NF-kappa B
Nitrites
Nitric Oxide Synthase
Superoxides
Transcription Factors
Western Blotting
Staining and Labeling

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

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Inhibition by (+/-)-indenestrol A of interferon gamma-stimulated nitric oxide formation in murine macrophage RAW 264.7 cells. / Oda, Taiko; So, You; Sato, Yoshihiro; Shimizu, Noriaki; Handa, Hiroshi; Yasukochi, Yukio; Kasahara, Tadashi.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 534, No. 1-2, 10.01.2003, p. 187-195.

Research output: Contribution to journalArticle

Oda, Taiko ; So, You ; Sato, Yoshihiro ; Shimizu, Noriaki ; Handa, Hiroshi ; Yasukochi, Yukio ; Kasahara, Tadashi. / Inhibition by (+/-)-indenestrol A of interferon gamma-stimulated nitric oxide formation in murine macrophage RAW 264.7 cells. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2003 ; Vol. 534, No. 1-2. pp. 187-195.
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AU - Handa, Hiroshi

AU - Yasukochi, Yukio

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