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Journal of Basic and Clinical Physiology and Pharmacology

Editor-in-Chief: Horowitz, Michal

Editorial Board: Das, Kusal K. / Epstein, Yoram / S. Gershon MD, Elliot / Kodesh , Einat / Kohen, Ron / Lichtstein, David / Maloyan, Alina / Mechoulam, Raphael / Roth, Joachim / Schneider, Suzanne / Shohami, Esther / Sohmer, Haim / Yoshikawa, Toshikazu / Tam, Joseph


CiteScore 2016: 1.01

SCImago Journal Rank (SJR) 2016: 0.349
Source Normalized Impact per Paper (SNIP) 2016: 0.495

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2191-0286
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Volume 28, Issue 6

Issues

The use of siRNA as a pharmacological tool to assess a role for the transcription factor NF-IL6 in the brain under in vitro and in vivo conditions during LPS-induced inflammatory stimulation

Jelena Damm
  • Department of Veterinary Physiology and Biochemistry, Justus-Liebig University Giessen, Giessen, Germany
  • Other articles by this author:
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/ Joachim Roth
  • Department of Veterinary Physiology and Biochemistry, Justus-Liebig University Giessen, Giessen, Germany
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/ Rüdiger Gerstberger
  • Department of Veterinary Physiology and Biochemistry, Justus-Liebig University Giessen, Giessen, Germany
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/ Christoph Rummel
  • Corresponding author
  • Department of Veterinary Physiology and Biochemistry, Justus-Liebig University Giessen, Giessen, Germany
  • Email
  • Other articles by this author:
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Published Online: 2017-08-18 | DOI: https://doi.org/10.1515/jbcpp-2017-0017

Abstract

Background:

Studies with NF-IL6-deficient mice indicate that this transcription factor plays a dual role during systemic inflammation with pro- and anti-inflammatory capacities. Here, we aimed to characterize the role of NF-IL6 specifically within the brain.

Methods:

In this study, we tested the capacity of short interfering (si) RNA to silence the inflammatory transcription factor nuclear factor-interleukin 6 (NF-IL6) in brain cells under in vitro and in vivo conditions.

Results:

In cells of a mixed neuronal and glial primary culture from the rat area postrema (AP), short interfering RNA (siRNA) directed against NF-IL6 strongly reduced basal and lipopolysaccharide (LPS)-induced nuclear immunoreactivity of this transcription factor, with the strongest effect on astrocytes. The siRNA did not exert inflammatory effects in the primary culture as confirmed by unaltered levels of IL-6 in supernatants. In vivo, intracerebroventricular (i.c.v.) injections of fluorochrome labelled siRNA caused its appearance in relevant brain structures for fever induction pathways such as the vascular organ of lamina terminalis, the subfornical organ, the median preoptic nucleus (MnPO) and the AP in several cell types, including microglial cells. However, i.c.v. injections of siRNA per se caused signs of fever, anorexia and reduced locomotor activity, i.e. sickness behavior.

Conclusions:

This approach was, thus, not suitable to characterize the role NF-IL6 in the brain in vivo, namely during experimentally induced systemic inflammation.

Keywords: fever; lipopolysaccharide; nuclear factor interleukin-6; siRNA

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About the article

Corresponding author: Dr. Christoph Rummel, Department of Veterinary Physiology and Biochemistry, Justus-Liebig-University Giessen, Frankfurter Str. 100, 35392 Giessen, Germany, Phone: +49-641-38155, Fax: +49-641-99-38159


Received: 2017-02-17

Accepted: 2017-06-02

Published Online: 2017-08-18

Published in Print: 2017-11-27


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: The study was supported by the Emmy Noether Program of the German Research Foundation (DFG project RU 1397/2-1).

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, Volume 28, Issue 6, Pages 563–571, ISSN (Online) 2191-0286, ISSN (Print) 0792-6855, DOI: https://doi.org/10.1515/jbcpp-2017-0017.

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