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

Publication ,  Journal Article
Guo, L; Guo, H; Gao, C; Mi, Z; Russell, WB; Kuo, PC
Published in: Surgery
August 2007

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 acetylated Stat1 by 5-fold (P < .02 vs control); TSA + IFN-gamma caused an additional 4-fold increase in acetylated Stat1 (P < .05 vs IFN alone). Stat1 binding to the iNOS promoter increased 8-fold with IFN-gamma (P < .01 vs control). In TSA + IFN-gamma, Stat1 binding was not different from controls. Although less potent than TSA, VPA also significantly decreased nitrite, iNOS protein, iNOS mRNA, Stat1 acetylation, and Stat1 binding. CONCLUSIONS: Acetylation of Stat1 protein correlates with decreased Stat1 binding to the iNOS promoter with resultant inhibition of IFN-gamma-mediated iNOS expression. Acetylation of the Stat1 protein may downregulate iNOS expression in proinflammatory states.

Duke Scholars

Published In

Surgery

DOI

ISSN

0039-6060

Publication Date

August 2007

Volume

142

Issue

2

Start / End Page

156 / 162

Location

United States

Related Subject Headings

  • Surgery
  • STAT1 Transcription Factor
  • Promoter Regions, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Nitric Oxide Synthase Type II
  • Mice
  • Macrophages
  • Interferon-gamma
  • Gene Expression Regulation, Enzymologic
  • Down-Regulation
 

Citation

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ICMJE
MLA
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Guo, L., Guo, H., Gao, C., Mi, Z., Russell, W. B., & Kuo, P. C. (2007). Stat1 acetylation inhibits inducible nitric oxide synthase expression in interferon-gamma-treated RAW264.7 murine macrophages. Surgery, 142(2), 156–162. https://doi.org/10.1016/j.surg.2007.02.016
Guo, Lucie, Hongtao Guo, Chengjiang Gao, Zhiyong Mi, William B. Russell, and Paul C. Kuo. “Stat1 acetylation inhibits inducible nitric oxide synthase expression in interferon-gamma-treated RAW264.7 murine macrophages.Surgery 142, no. 2 (August 2007): 156–62. https://doi.org/10.1016/j.surg.2007.02.016.
Guo, Lucie, et al. “Stat1 acetylation inhibits inducible nitric oxide synthase expression in interferon-gamma-treated RAW264.7 murine macrophages.Surgery, vol. 142, no. 2, Aug. 2007, pp. 156–62. Pubmed, doi:10.1016/j.surg.2007.02.016.
Journal cover image

Published In

Surgery

DOI

ISSN

0039-6060

Publication Date

August 2007

Volume

142

Issue

2

Start / End Page

156 / 162

Location

United States

Related Subject Headings

  • Surgery
  • STAT1 Transcription Factor
  • Promoter Regions, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Nitric Oxide Synthase Type II
  • Mice
  • Macrophages
  • Interferon-gamma
  • Gene Expression Regulation, Enzymologic
  • Down-Regulation