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Nitric oxide down-regulates hepatocyte-inducible nitric oxide synthase gene expression
1Department of Surgery, University of Pittsburgh, Pa., USA.
Archives of Surgery (Chicago, Ill. : 1960)
|November 21, 1997
Summary
Nitric oxide (NO) down-regulates inducible nitric oxide synthase (iNOS) gene transcription by inhibiting NF-kappa B activity. This finding reveals a novel negative feedback mechanism to limit iNOS overproduction during sepsis.
Area of Science:
- Molecular biology
- Sepsis research
- Immunology
Background:
- Inducible nitric oxide synthase (iNOS) expression is implicated in the systemic effects of sepsis.
- Understanding the regulation of iNOS is crucial for managing sepsis.
Purpose of the Study:
- To investigate if nitric oxide (NO) negatively regulates iNOS gene expression.
- To elucidate the molecular mechanisms behind NO's potential regulatory role.
Main Methods:
- Primary rat hepatocytes were cultured with a cytokine mix.
- The effect of an NO donor on iNOS mRNA, protein, and enzyme activity was assessed.
- NF-kappa B DNA binding activity was analyzed using electrophoretic mobility shift assays.
Main Results:
- NO significantly reduced iNOS mRNA and protein levels.
- NF-kappa B DNA binding activity was decreased in a dose-dependent manner by NO.
- NO did not inhibit iNOS enzyme activity.
Conclusions:
- NO down-regulates iNOS gene transcription, partly by inhibiting NF-kappa B.
- This represents a novel negative feedback loop to control iNOS production during sepsis.