Stat1 acetylation inhibits inducible nitric oxide synthase expression in interferon-gamma-treated RAW264.7 murine macrophages.

ABSTRACT:

Background

We hypothesized that acetylation of the Stat1 regulates interferon-gamma (IFN-gamma) mediated macrophage expression of inducible nitric oxide synthase (iNOS).

Methods

RAW 264.7 iNOS expression was induced with IFN-gamma. Deacetylase inhibitors trichostatin A (TSA) or valproic acid (VPA) were added. Stat1 and iNOS mRNA and protein were measured. Acetylated Stat1 was determined by immunoprecipitation. Chromatin immunoprecipitation assessed in vivo binding of Stat1 to the iNOS promoter.

Results

IFN-gamma significantly increased nitrite, iNOS protein and iNOS mRNA, and iNOS promoter activation. (P < .01 vs control for nitrite, protein, and mRNA). TSA-mediated acetylation decreased these to levels that were not different from controls. IFN-gamma increased acetyl

SUBMITTER: Guo L 

PROVIDER: S-EPMC2034510 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature