Interleukin 1β inhibits interleukin 6-mediated rat γ fibrinogen gene expression

Zhixin Zhang, Gerald M. Fuller

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Interleukin (IL)-1β and IL-6 are the 2 major inducers of a group of hepatic genes during acute inflammation; however, each cytokine uses different intracellular signaling molecules. In most instances, the 2 cytokines interect positively to enhance hepatic gene expression, but in one class of acute-phase reactants, which includes fibrinogen, IL-1β exerts a transient inhibitory effect over the IL-6 stimulatory signal. This study explored the effects of IL-1β/nuclear factor κB (NF-κB) and IL-6/signal transducer and activator of transcription 3 (STAT3) combinatory signaling on the transcriptional regulation of the rat γ fibrinogen gene. Northern blot and functional analyses employing luciferase reporter constructs driven by the rat γ fibrinogen promoter demonstrated that IL-1β inhibited the IL-6-mediated transcription of this gene. Exposing primary rat hepatocytes to IL-1β had no effect on IL-6-mediated STAT3 activation; instead, IL-1β-activated NF-κB associated with 2 IL-6 responsive elements (STAT3 binding site) on the rat γ fibrinogen promoter and blocked STAT3 binding to these regions. The competitive binding of NF-κB and STAT3 on the overlapping binding site provides a mechanism for the inhibition by IL-1β of the IL-6-mediated transactivation of rat γ fibrinogen. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)3466-3472
Number of pages7
JournalBlood
Volume96
Issue number10
DOIs
StatePublished - Nov 15 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Interleukin 1β inhibits interleukin 6-mediated rat γ fibrinogen gene expression'. Together they form a unique fingerprint.

Cite this