2-Aminopurine inhibits lipopolysaccharide-induced nitric oxide production by preventing IFN-β production

Tsuyoshi Sugiyama, Megumi Fujita, Naoki Koide, Isamu Mori, Tomoaki Yoshida, Hiroshi Mori, Takashi Yokochi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

2-Aminopurine (2-AP) is widely used as a specific inhibitor for double stranded-RNA dependent protein kinase (PKR). Here we report that 2-AP can inhibit lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production through the prevention of interferon (IFN)-β production. 2-AP significantly inhibited NO production in LPS-stimulated RAW 264 murine macrophage cells. 2-AP also reduced the expression of IFN-β and IFN-inducible genes, such as IFN-γ-inducible protein (IP)-10 and immune-responsive gene (IRG)-1, and the inducible type of NO synthase (iNOS) mRNA in response to LPS. The addition of exogenous IFN-β restored 2-AP-inhibited NO production in response to LPS. On the other hand, there was only partial inhibition by 2-AP of nuclear factor (NF)-κB activation, IL-6 mRNA expression and tumor necrosis factor (TNF)-α production. These results suggested that 2-AP inhibited LPS-induced IFN-β production by preventing Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF)-dependent signaling rather than myeloid differentiation factor (MyD) 88-dependent signaling, resulting in the inhibition of NO production.

Original languageEnglish
Pages (from-to)957-963
Number of pages7
JournalMICROBIOLOGY and IMMUNOLOGY
Volume48
Issue number12
DOIs
Publication statusPublished - 2004

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Virology

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