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      Baicalein attenuates OVA-induced allergic airway inflammation through the inhibition of the NF-κB signaling pathway

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          Abstract

          Asthma is a type of chronic lung inflammation with restrictions in effective therapy. NF-κB pathway activation has been suggested to play an important role in the pathogenesis of asthma. Baicalein, one of the major active flavonoids found in Scutellaria baicalensis, exhibits potent anti-inflammatory properties by inhibiting NF-κB activity. Herein, we report that Baicalein significantly reduces OVA-induced airway hyperresponsiveness (AHR), airway inflammation, serum IgE levels, mucus production, and collagen deposition around the airway. Additionally, western blot analysis and immunofluorescence assay showed that Baicalein attenuates the activation of NF-κB, which was mainly reflected by IκBα phosphorylation and degradation, p65 nuclear translocation and downstream iNOS expression. Furthermore, in human epithelial cells, Baicalein blocked TNF-α-induced NF-κB activation. Our study provides evidence that Baicalein administration alleviates the pathological changes in asthma through inactivating the NF-κB/iNOS pathway. Baicalein might be a promising potential therapy agent for patients with allergic asthma in the future.

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          Muc5b is required for airway defence.

          Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b(-/-) mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.
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            Asthma and allergic inflammation.

            Studies of the initiation and maintenance of asthma and allergic inflammation implicate dysregulated interactions between mucosal epithelia and innate immune cells as the underlying cause of these disorders. The similarities of these responses with mucosal responses to parasitic intestinal worms may reveal pathways relevant to the perplexing rise of these chronic inflammatory disorders. 2010 Elsevier Inc. All rights reserved.
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              The Biology of Eosinophils and Their Role in Asthma

              This review will describe the structure and function of the eosinophil. The roles of several relevant cell surface molecules and receptors will be discussed. We will also explore the systemic and local processes triggering eosinophil differentiation, maturation, and migration to the lungs in asthma, as well as the cytokine-mediated pathways that result in eosinophil activation and degranulation, i.e., the release of multiple pro-inflammatory substances from eosinophil-specific granules, including cationic proteins, cytokines, chemokines growth factors, and enzymes. We will discuss the current understanding of the roles that eosinophils play in key asthma processes such as airway hyperresponsiveness, mucus hypersecretion, and airway remodeling, in addition to the evidence relating to eosinophil–pathogen interactions within the lungs.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                15 November 2019
                06 November 2019
                : 11
                : 21
                : 9310-9327
                Affiliations
                [1 ]The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
                [2 ]Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
                [3 ]Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, China
                [4 ]Department of Pharmacology and Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou, China
                Author notes
                [*]

                Equal contribution

                Correspondence to: Songmin Ying; email: yings@zju.edu.cn
                Correspondence to: Yali Zhang; email: ya-li000@163.com
                Correspondence to: Yuanrong Dai; email: daiyr@126.com
                Article
                102371 102371
                10.18632/aging.102371
                6874438
                31692453
                6515b65c-072d-4c70-aeaa-4fc9abdd2f2b
                Copyright © 2019 Xu et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 09 June 2018
                : 12 October 2019
                Categories
                Research Paper

                Cell biology
                baicalein,asthma,inflammation,nf-κb,inos
                Cell biology
                baicalein, asthma, inflammation, nf-κb, inos

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