Induced nitric oxide inhibits IL-6-induced Stat3 activation and type II acute phase mRNA expression

Raphael T. Villavicencio, Shubing Liu, Melina R. Kibbe, Debra L. Williams, Raymond W. Ganster, Kevin F. Dyer, David J. Tweardy, Timothy R. Billiar, Bruce R. Pitt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Inducible nitric oxide synthase (iNOS) can be coexpressed with acute phase reactants in hepatocytes; however, it is unknown if NO can regulate the acute phase response. We tested the hypothesis that iNOS-derived nitric oxide (NO) attenuates the acute phase response by inhibiting IL-6-enhanced Stat3 DNA-binding activity and type II acute phase mRNA expression. iNOS was overexpressed in cultured rat hepatocytes via transduction with a replication defective adenovirus containing cDNA for human iNOS (AdiNOS), and Stat3 DNA-binding activity was determined by electrophoretic mobility shift assay (EMSA). EMSAs demonstrated that AdiNOS inhibits IL-6-induced Stat3 activation and that this inhibition is reversible in the presence of the NOS inhibitor NG-monomethyl-L-arginine (L-NMA). The induction of β-fibrinogen mRNA by IL-6, a Stat3 dependent process, is attenuated in AdiNOS-transduced cells and partially reversed by L-NMA. Thus, iNOS overexpression suppresses IL-6-induced Stat3 activation and type II acute phase mRNA expression in cultured hepatocytes. This suppression may represent a mechanism by which NO down-regulates the acute phase response.

Original languageEnglish (US)
Pages (from-to)441-445
Number of pages5
JournalShock
Volume13
Issue number6
DOIs
StatePublished - Jun 2000

Keywords

  • Adenoviral vector
  • Hepatocytes
  • Inducible nitric oxide synthase
  • Interleukin 6
  • Stat3
  • β-fibrinogen

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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