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

4 Citations (Scopus)

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)-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.

Original languageEnglish
Pages (from-to)187-195
Number of pages9
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume534
Issue number1-2
DOIs
Publication statusPublished - 2003 Jan 10

Fingerprint

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

Keywords

  • Apoptosis
  • IFN-γ
  • Indenestrol A
  • Nitric oxide
  • RAW 264.7

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics

Cite this

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 - Genetic Toxicology and Environmental 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 - Genetic Toxicology and Environmental Mutagenesis. 2003 ; Vol. 534, No. 1-2. pp. 187-195.
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