关键词: MAVS cytokine feruloylated oligosaccharides influenza lung inflammation

Mesh : Animals Mice Oligosaccharides / administration & dosage chemistry pharmacology Orthomyxoviridae Infections / immunology prevention & control metabolism Influenza A Virus, H1N1 Subtype / immunology Humans Mice, Knockout Signal Transduction / drug effects immunology Influenza, Human / immunology prevention & control metabolism TNF Receptor-Associated Factor 3 / genetics metabolism immunology DEAD Box Protein 58 / genetics metabolism immunology Pneumonia / immunology prevention & control metabolism virology Mice, Inbred C57BL Lung / immunology metabolism drug effects virology Cytokines / metabolism immunology genetics Female NF-kappa B / immunology genetics metabolism Anti-Inflammatory Agents / administration & dosage pharmacology

来  源:   DOI:10.1021/acs.jafc.3c09390

Abstract:
Uncontrolled inflammation contributes significantly to the mortality in acute respiratory infections. Our previous research has demonstrated that maize bran feruloylated oligosaccharides (FOs) possess notable anti-inflammatory properties linked to the NF-kB pathway regulation. In this study, we clarified that the oral administration of FOs moderately inhibited H1N1 virus infection and reduced lung inflammation in influenza-infected mice by decreasing a wide spectrum of cytokines (IFN-α, IFN-β, IL-6, IL-10, and IL-23) in the lungs. The mechanism involves FOs suppressing the transduction of the RIG-I/MAVS/TRAF3 signaling pathway, subsequently lowering the expression of NF-κB. In silico analysis suggests that FOs have a greater binding affinity for the RIG-I/MAVS signaling complex. This indicates that FOs have potential as promising targets for immune modulation. Moreover, in MAVS knockout mice, we confirmed that the anti-inflammatory function of FOs against influenza depends on MAVS. Comprehensive analysis using 16S rRNA gene sequencing and metabolite profiling techniques showed that FOs have the potential to restore immunity by modulating the gut microbiota. In conclusion, our study demonstrates that FOs are effective anti-inflammatory phytochemicals in inhibiting lung inflammation caused by influenza. This suggests that FOs could serve as a potential nutritional strategy for preventing the H1N1 virus infection and associated lung inflammation.
摘要:
不受控制的炎症显著导致急性呼吸道感染的死亡率。我们先前的研究表明,玉米麸皮阿魏酸化寡糖(FOs)具有与NF-kB途径调节相关的显着抗炎特性。在这项研究中,我们阐明,口服FOs可通过减少广泛的细胞因子(IFN-α,IFN-β,IL-6,IL-10和IL-23)在肺中。其机制涉及FOs抑制RIG-I/MAVS/TRAF3信号通路的转导,随后降低NF-κB的表达。计算机模拟分析表明FOs对RIG-I/MAVS信号传导复合物具有更大的结合亲和力。这表明FOs具有作为免疫调节的有希望的靶标的潜力。此外,在MAVS基因敲除小鼠中,我们证实FOs抗流感的抗炎功能取决于MAVS。使用16SrRNA基因测序和代谢物谱分析技术的综合分析表明,FOs具有通过调节肠道微生物群恢复免疫力的潜力。总之,我们的研究表明,FOs是有效的抗炎植物化学物质,可以抑制流感引起的肺部炎症。这表明FOs可以作为预防H1N1病毒感染和相关肺部炎症的潜在营养策略。
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