Type I interferon supports inducible nitric oxide synthase in murine hepatoma cells and hepatocytes and during experimental acetaminophen-induced liver damage

  • Cytokine regulation of high-output nitric oxide (NO) derived from inducible NO synthase (iNOS) is critically involved in inflammation biology and host defense. Herein, we set out to characterize the role of type I interferon (IFN) as potential regulator of hepatic iNOS in vitro and in vivo. In this regard, we identified in murine Hepa1-6 hepatoma cells a potent synergism between pro-inflammatory interleukin-β/tumor necrosis factor-α and immunoregulatory IFNβ as detected by analysis of iNOS expression and nitrite release. Upregulation of iNOS by IFNβ coincided with enhanced binding of signal transducer and activator of transcription-1 to a regulatory region at the murine iNOS promoter known to support target gene expression in response to this signaling pathway. Synergistic iNOS induction under the influence of IFNβ was confirmed in alternate murine Hepa56.1D hepatoma cells and primary hepatocytes. To assess iNOS regulation by type I IFN in vivo, murine acetaminophen (APAP)-induced sterile liver inflammation was investigated. In this model of acute liver injury, excessive necroinflammation drives iNOS expression in diverse liver cell types, among others hepatocytes. Herein, we demonstrate impaired iNOS expression in type I IFN receptor-deficient mice which associated with diminished APAP-induced liver damage. Data presented indicate a vital role of type I IFN within the inflamed liver for fine-tuning pathological processes such as overt iNOS expression.

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Author:Malte Bachmann, Zoe Waibler, Thomas Pleli, Josef Martin PfeilschifterGND, Heiko Mühl
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/28824623
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Claudia Ursula Dürr
Document Type:Article
Year of Completion:2017
Date of first Publication:2017/07/31
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/04/26
Tag:acetaminophen; inducible nitric oxide synthase; liver damage; signal transducer and activator of transcription-1; type I interferon
Issue:Art. 890
Page Number:11
First Page:1
Last Page:11
Copyright: © 2017 Bachmann, Waibler, Pleli, Pfeilschifter and Mühl. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Institutes:Biowissenschaften / Biowissenschaften
Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0