Dataset Information

NF-κB signaling in tanycytes mediates inflammation-induced anorexia.

ABSTRACT:

Objectives

Infections, cancer, and systemic inflammation elicit anorexia. Despite the medical significance of this phenomenon, the question of how peripheral inflammatory mediators affect the central regulation of food intake is incompletely understood. Therefore, we have investigated the sickness behavior induced by the prototypical inflammatory mediator IL-1β.

Methods

IL-1β was injected intravenously. To interfere with IL-1β signaling, we deleted the essential modulator of NF-κB signaling (Nemo) in astrocytes and tanycytes.

Results

Systemic IL-1β increased the activity of the transcription factor NF-κB in tanycytes of the mediobasal hypothalamus (MBH). By activating NF-κB signaling, IL-1β induced the expression of cyclooxygenase-2 (Cox-2) and stimulated the release of the anorexigenic prostaglandin E₂ (PGE₂) from tanycytes. When we deleted Nemo in astrocytes and tanycytes, the IL-1β-induced anorexia was alleviated whereas the fever response and lethargy response were unchanged. Similar results were obtained after the selective deletion of Nemo exclusively in tanycytes.

Conclusions

Tanycytes form the brain barrier that mediates the anorexic effect of systemic inflammation in the hypothalamus.

SUBMITTER: Bottcher M

PROVIDER: S-EPMC7292913 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

NF-κB signaling in tanycytes mediates inflammation-induced anorexia.

Böttcher Mareike M Müller-Fielitz Helge H Sundaram Sivaraj M SM Gallet Sarah S Neve Vanessa V Shionoya Kiseko K Zager Adriano A Quan Ning N Liu Xiaoyu X Schmidt-Ullrich Ruth R Haenold Ronny R Wenzel Jan J Blomqvist Anders A Engblom David D Prevot Vincent V Schwaninger Markus M

Molecular metabolism 20200521

<h4>Objectives</h4>Infections, cancer, and systemic inflammation elicit anorexia. Despite the medical significance of this phenomenon, the question of how peripheral inflammatory mediators affect the central regulation of food intake is incompletely understood. Therefore, we have investigated the sickness behavior induced by the prototypical inflammatory mediator IL-1β.<h4>Methods</h4>IL-1β was injected intravenously. To interfere with IL-1β signaling, we deleted the essential modulator of NF-κB ...[more]

PMID: 32446877

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Project description:ObjectivesBiosurfactants with anti-inflammatory activity may alleviate skin irritation caused by synthetic surfactants in cleaning products. Sophorolipid (SL) is a promising alternative to synthetic surfactants. However, there are few reports on the anti-inflammatory activity of SL and the underlying mechanism. The purpose of this work is to verify that lipopolysaccharide (LPS)-induced inflammation could be inhibited through targeting the pathway of nuclear factor-κB (NF-κB) in RAW264.7 cells.MethodsThe influence of SL on cytokine release was investigated by LPS-induced RAW264.7 cells using ELISA. The quantification of the protein expression of corresponding molecular markers was realized by Western blot analysis. Flow cytometry was employed to determine the levels of Ca2+ and reactive oxygen species (ROS). The relative expression of inducible nitric oxide synthase (INOS) and cyclooxygenase-2 (COX-2) was determined by RT-PCR. An immunofluorescence assay and confocal microscope were used to observe the NF-κB/p65 translocation from the cytoplasm into the nucleus. The likely targets of SL were predicted by molecular docking analysis.ResultsSL showed anti-inflammatory activity and reduced the release of inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO). The experimental results show that SL suppressed the Ca2+ and ROS levels influx in the LPS-induced RAW264.7 cells and alleviated the LPS-induced expression of iNOS and COX-2, the LPS-induced translocation of NF-κB (p65) from the cytoplasm into the nucleus, and the expression of phosphorylated proteins such as p65 and IκBα. Furthermore, molecular docking analysis showed that SL may inhibit inflammatory signaling by competing with LPS to bind TLR4/MD-2 through hydrophobic interactions and by inhibiting IKKβ activation through the hydrogen bonding and hydrophobic interactions.ConclusionThis study demonstrated that SL exerted anti-inflammatory activity via the pathway of NF-κB in RAW264.7 cells.

Dataset Information

NF-κB signaling in tanycytes mediates inflammation-induced anorexia.

Objectives

Methods

Results

Conclusions

Publications

NF-κB signaling in tanycytes mediates inflammation-induced anorexia.

Similar Datasets

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