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.
Acknowledgments
We would like to thank D. Marks, D. Ott and J. Murgott for excellent technical assistance.
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.
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