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Induced nitric oxide inhibits IL-6-induced stat3 activation and type II acute phase mRNA expression
R T Villavicencio1, S Liu, M R Kibbe
1Department of Surgery, University of Pittsburgh, Pennsylvania 15261, USA.
Shock (Augusta, Ga.)
|June 10, 2000
Summary
Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) suppresses the acute phase response by inhibiting IL-6-induced Stat3 activation and acute phase mRNA expression in hepatocytes.
Area of Science:
- Hepatology
- Molecular Biology
- Immunology
Background:
- Inducible nitric oxide synthase (iNOS) is coexpressed with acute phase reactants in hepatocytes.
- The role of nitric oxide (NO) in regulating the acute phase response remains unclear.
Purpose of the Study:
- To investigate if iNOS-derived NO attenuates the acute phase response.
- To determine if NO inhibits IL-6-enhanced Stat3 DNA-binding activity and type II acute phase mRNA expression.
Main Methods:
- Overexpression of iNOS in cultured rat hepatocytes using adenovirus (AdiNOS).
- Assessment of Stat3 DNA-binding activity via electrophoretic mobility shift assay (EMSA).
- Measurement of beta-fibrinogen mRNA induction by IL-6.
Main Results:
- AdiNOS inhibited IL-6-induced Stat3 activation in a reversible manner with N(G)-monomethyl-L-arginine (L-NMA).
- IL-6-induced beta-fibrinogen mRNA expression, a Stat3-dependent process, was attenuated in AdiNOS-transduced cells.
- L-NMA partially reversed the inhibitory effects of AdiNOS.
Conclusions:
- iNOS overexpression suppresses IL-6-induced Stat3 activation and type II acute phase mRNA expression in hepatocytes.
- NO may represent a mechanism for down-regulating the acute phase response.