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Interleukin-28B dampens airway inflammation through up-regulation of natural killer cell-derived IFN-?.

ABSTRACT: Interleukin-28A (IL-28A) modulates CD11c+ dendritic cell (DC) function and promotes type 1T helper (Th1) differentiation, thus suppressing allergic airway diseases. However, the function of the IL-28A isoform IL-28B in these diseases remains largely unknown. In this study, we revealed a novel role of IL-28B in inducing type 1 immunity and protecting against ovalbumin (OVA)-induced allergic asthma in mice. IL-28B overexpression in wild-type mice promoted natural killer (NK) cell polarization in the lung, leading to the increased number of interferon (IFN)-?-producing NK1 cells as well as Th1 differentiation. Importantly, IL-28B overexpression had no protective effect on OVA-induced asthma in IFN-?-knockout (IFN-?-/-) mice. These results demonstrate that IL-28B ameliorates experimental allergic asthma via enhancing NK cell polarization, which might be useful for prevention and treatment of allergic asthma.

SUBMITTER: Yan B

PROVIDER: S-EPMC5472588 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Interleukin-28B dampens airway inflammation through up-regulation of natural killer cell-derived IFN-γ.

Yan Bailing B Chen Feng F Xu Lijun L Wang Yanshi Y Wang Xuefu X

Scientific reports 20170615 1

Interleukin-28A (IL-28A) modulates CD11c+ dendritic cell (DC) function and promotes type 1T helper (Th1) differentiation, thus suppressing allergic airway diseases. However, the function of the IL-28A isoform IL-28B in these diseases remains largely unknown. In this study, we revealed a novel role of IL-28B in inducing type 1 immunity and protecting against ovalbumin (OVA)-induced allergic asthma in mice. IL-28B overexpression in wild-type mice promoted natural killer (NK) cell polarization in t ...[more]

PMID: 28620197

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Project description:BACKGROUND:Chronic respiratory diseases, whose one of the hallmarks is oxidative stress, are still incurable and need novel therapeutic tools and pharmaceutical agents. The phenolic compounds contained in grape are endowed with well-recognized anti-oxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Considering that natural anti-oxidants, such as proanthocyanidins, have poor water solubility and oral bioavailability, we have developed a drug delivery system based on solid lipid nanoparticles (SLN), apt to encapsulate grape seed extract (GSE), containing proanthocyanidins. METHODS:Plain, 6-coumarin (6-Coum), DiR- and GSE-loaded SLN were produced with the melt-emulsion method. Physicochemical characterization of all prepared SLN was determined by photon correlation spectroscopy and laser Doppler anemometry. MTT assay (spectrophotometry) and propidium iodide (PI) assay (cytofluorimetry) were used to assess cell viability. Flow cytometry coupled with cell imaging was performed for assessing apoptosis and necrosis by Annexin V/7-AAD staining (plain SLE), cell internalization (6-Coum-SLN) and reactive oxygen species (ROS) production (SLN-GSE). NF-κB nuclear translocation was studied by immunofluorescence. In vivo bio-imaging was used to assess lung deposition and persistence of aerosolized DiR-loaded SLN. RESULTS:Plain SLN were not cytotoxic when incubated with H441 airway epithelial cells, as judged by both PI and MTT assays as well as by apoptosis/necrosis evaluation. 6-Coum-loaded SLN were taken up by H441 cells in a dose-dependent fashion and persisted into cells at detectable levels up to 16 days. SLN were detected in mice lungs up to 6 days. SLN-GSE possessed 243 nm as mean diameter, were negatively charged, and stable in size at 37 °C in Simulated Lung Fluid up to 48 h and at 4 °C in double distilled water up to 2 months. The content of SLN in proanthocyanidins remained unvaried up to 2 months. GSE-loaded SLN determined a significant reduction in ROS production when added 24-72 h before the stimulation with hydrogen peroxide. Interestingly, while at 24 h free GSE determined a higher decrease of ROS production than SLN-GSE, the contrary was seen at 48 and 72 h. Similar results were observed for NF-κB nuclear translocation. CONCLUSIONS:SLN are a biocompatible drug delivery system for natural anti-oxidants obtained from grape seed in a model of oxidative stress in airway epithelial cells. They feature stability and long-term persistence inside cells where they release proanthocyanidins. These results could pave the way to novel anti-oxidant and anti-inflammatory therapies for chronic respiratory diseases.

Dataset Information

Interleukin-28B dampens airway inflammation through up-regulation of natural killer cell-derived IFN-?.

Publications

Interleukin-28B dampens airway inflammation through up-regulation of natural killer cell-derived IFN-γ.

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