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Endotoxin-mediated nitric oxide synthesis inhibits IL-1beta gene transcription in ANA-1 murine macrophages.

Publication ,  Journal Article
Schroeder, RA; Cai, C; Kuo, PC
Published in: Am J Physiol
September 1999

On the basis of previous work demonstrating nitric oxide (NO)-mediated inhibition of nuclear factor-kappaB (NF-kappaB) DNA binding, we hypothesized that NO downregulates NF-kappaB-dependent interleukin-1beta (IL-1beta) production in an ANA-1 macrophage model of lipopolysaccharide (LPS) stimulation. In the presence of LPS (100 ng/ml), levels of IL-1beta protein and mRNA were significantly upregulated with NO synthase inhibition. Using nuclear run-on analysis and transient transfection studies, IL-1beta gene transcription and IL-1beta promoter activity were also found to be increased with inhibition of NO production. Parallel transfection studies using an NF-kappaB long terminal repeat-reporter plasmid exhibited similar findings, suggesting an NO-mediated effect on NF-kappaB activity. Gel shift studies showed that LPS-associated NF-kappaB DNA binding was increased, both in the setting of NO synthase inhibition and in a reducing environment. Repletion of NO by addition of an S-nitrosothiol restored IL-1beta protein synthesis, mRNA levels, gene transcription, promoter activity, and NF-kappaB DNA binding to levels noted in the presence of LPS alone. Our studies indicate that NO may regulate LPS-associated inflammation by downregulating IL-1beta gene transcription through S-nitrosation of NF-kappaB.

Duke Scholars

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

September 1999

Volume

277

Issue

3

Start / End Page

C523 / C530

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • S-Nitrosothiols
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Nitroso Compounds
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Nitric Oxide Donors
  • Nitric Oxide
 

Citation

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ICMJE
MLA
NLM
Schroeder, R. A., Cai, C., & Kuo, P. C. (1999). Endotoxin-mediated nitric oxide synthesis inhibits IL-1beta gene transcription in ANA-1 murine macrophages. Am J Physiol, 277(3), C523–C530. https://doi.org/10.1152/ajpcell.1999.277.3.C523
Schroeder, R. A., C. Cai, and P. C. Kuo. “Endotoxin-mediated nitric oxide synthesis inhibits IL-1beta gene transcription in ANA-1 murine macrophages.Am J Physiol 277, no. 3 (September 1999): C523–30. https://doi.org/10.1152/ajpcell.1999.277.3.C523.
Schroeder, R. A., et al. “Endotoxin-mediated nitric oxide synthesis inhibits IL-1beta gene transcription in ANA-1 murine macrophages.Am J Physiol, vol. 277, no. 3, Sept. 1999, pp. C523–30. Pubmed, doi:10.1152/ajpcell.1999.277.3.C523.
Schroeder RA, Cai C, Kuo PC. Endotoxin-mediated nitric oxide synthesis inhibits IL-1beta gene transcription in ANA-1 murine macrophages. Am J Physiol. 1999 Sep;277(3):C523–C530.

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

September 1999

Volume

277

Issue

3

Start / End Page

C523 / C530

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • S-Nitrosothiols
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Nitroso Compounds
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Nitric Oxide Donors
  • Nitric Oxide