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      Perilla Leaf Extract Attenuates Asthma Airway Inflammation by Blocking the Syk Pathway

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          Abstract

          Perilla frutescens (L.) Britton is a classic herbal plant used widely against asthma in China. But its mechanism of beneficial effect remains undermined. In the study, the antiallergic asthma effects of Perilla leaf extract (PLE) were investigated, and the underlying mechanism was also explored. Results showed that PLE treatment significantly attenuated airway inflammation in OVA-induced asthma mice, by ameliorating lung pathological changes, inhibiting recruitment of inflammatory cells in lung tissues and bronchoalveolar lavage fluid (BALF), decreasing the production of inflammatory cytokines in the BALF, and reducing the level of immunoglobulin in serum. PLE treatment suppressed inflammatory response in antigen-induced rat basophilic leukemia 2H3 (RBL-2H3) cells as well as in OVA-induced human peripheral blood mononuclear cells (PBMCs). Furthermore, PLE markedly inhibited the expression and phosphorylation of Syk, NF- κB, PKC, and cPLA 2 both in vivo and in vitro. By cotreating with inhibitors (BAY61-3606, Rottlerin, BAY11-7082, and arachidonyl trifluoromethyl ketone) in vitro, results revealed that PLE's antiallergic inflammatory effects were associated with the inhibition of Syk and its downstream signals NF- κB, PKC, and cPLA 2. Collectively, the present results suggested that PLE could attenuate allergic inflammation, and its mechanism might be partly mediated through inhibiting the Syk pathway.

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          Most cited references32

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          NF-kappaB Signaling in Chronic Inflammatory Airway Disease

          Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments. In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression. The redox-sensitive transcription factor, nuclear factor (NF)-kappaB (NF-κB), is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology. The anti-inflammatory actions of glucocorticoids (GCs), a mainstay treatment for asthma, involve inhibition of NF-κB induced gene transcription. Ligand bound GC receptors (GRs) bind NF-κB to suppress the transcription of NF-κB responsive genes (i.e., transrepression). However, in severe asthma and COPD, the transrepression of NF-κB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling. Therapeutics which target NF-κB activation, including inhibitors of IκB kinases (IKKs) are potential treatments for asthma and COPD. Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-κB transrepression. This review examines NF-κB signaling in airway inflammation and its potential as target for treatment of asthma and COPD.
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            Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

            Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk) was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases.
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              Inhaled Corticosteroids Safety and Adverse Effects in Patients with Asthma

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                Author and article information

                Contributors
                Journal
                Mediators Inflamm
                Mediators Inflamm
                mi
                Mediators of Inflammation
                Hindawi
                0962-9351
                1466-1861
                2021
                10 May 2021
                : 2021
                : 6611219
                Affiliations
                1State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
                2Beijing Friendship Hospital, Capital Medical University, Beijing, China
                Author notes

                Academic Editor: Raffaele Capasso

                Author information
                https://orcid.org/0000-0002-1139-4573
                https://orcid.org/0000-0002-7636-448X
                https://orcid.org/0000-0003-0226-5443
                Article
                10.1155/2021/6611219
                8128618
                34045925
                f75e0a73-3b6d-4a6b-a05d-19f7eb83eae3
                Copyright © 2021 Hui Yang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 January 2021
                : 2 April 2021
                : 20 April 2021
                Funding
                Funded by: PUMC Graduate Innovation Fund
                Award ID: 2019-1007-14
                Funded by: Drug Innovation Major Project of China
                Award ID: 2018ZX09711001-003-001
                Funded by: Chinese Academy of Medical Sciences
                Award ID: 2016-I2M-2-006
                Funded by: Beijing Municipal Natural Science Foundation
                Award ID: 7182116
                Funded by: National Natural Science Foundation of China
                Award ID: 81803810
                Award ID: 81473398
                Award ID: 81973539
                Categories
                Research Article

                Immunology
                Immunology

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