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Laccase/caffeic acid-catalyzed crosslinking coupled with galactomannan alters the conformational structure of ovalbumin and alleviates Th2-mediated allergic asthma

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Food Science and Human Wellness 2024年第4期13卷 1962-1973页

作者： Ishfaq Ahmed suidong ouyang Shengquan Wu Haochang Song Miaoyuan Zhang Renxing Luo Peishan Lu Jiaqi Deng Tingting Zheng Yanyan Wang Xinguang Liu Gonghua Huang Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan 523808China Haide College Ocean University of ChinaLaoshan CampusQingdao 266100China School of Medical Technology Guangdong Medical UniversityDongguan 523808China

Ovalbumin(OVA)is the major allergenic protein that can induce T helper 2(Th2)-allergic reactions,for which current treatment options are inadequate.In this study,we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid(Lac/CA)-catalyzed crosslinking in conjunction with galactomannan(Man).The formation of high molecular weight crosslinked polymers and the Ig G-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting.The study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface hydrophobicity.Gastrointestinal digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid(SGF)and simulated intestinal fluid(SIF).Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines(interleukin(IL)-4,IL-5,and IL-13),and upregulated IFN-γand IL-10 expression.Stimulation of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers(CD80 and CD86)and MHC class II molecules,and suppressed the expression levels of proinflammatory cytokines.The knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.

关键词： Ovalbumin Laccase Galactomannan Conformational structure Asthma

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The kinase p38αfunctions in dendritic cells to regulate Th2-cell differentiation and allergic inflammation

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Cellular & Molecular Immunology 2022年第7期19卷 805-819页

作者： Miaomiao Han Jingyu Ma suidong ouyang Yanyan Wang Tingting Zheng Peishan Lu Zihan Zheng Weiheng Zhao Hongjin Li Yun Wu Baohua Zhang Ran Hu Kinya Otsu Xinguang Liu Ying Wan Huabin Li Gonghua Huang ENT Institute and Department of Otorhinolaryngology Eye&ENT HospitalFudan University200031 ShanghaiChina Shanghai Institute of Immunology Shanghai Jiao Tong University School of Medicine200025 ShanghaiChina Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics Guangdong Medical University523808 DongguanChina Biomedical Analysis Center Army Medical University400038 ChongqingChina Department of Cardiovascular Medicine Graduate School of MedicineOsaka UniversityOsaka 565-0871Japan School of Cardiovascular Medicine and Sciences King’s College LondonLondon SE59NUUK Present address:Tongji Hospital Tongji Medical CollegeHuazhong University of Science and Technology430030 WuhanChina Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese Medicine200437 ShanghaiChina Department of Clinical Laboratory Medicine Shanghai Tenth People’s Hospital of Tongji University200072 ShanghaiChina Present address:Basic Department of Cancer Center Shanghai Tenth People’s Hospital of Tongji University200072 ShanghaiChina

Dendritic cells(DCs)play a critical role in controlling T helper 2(Th2)cell-dependent diseases,but the signaling mechanism that triggers this function is not fully understood.We showed that p38αactivity in DCs was decreased upon HDM stimulation and dynamically regulated by both extrinsic signals and Th2-instructive cytokines.p38α-specific deletion in cDC1s but not in cDC2s or macrophages promoted Th2 responses under HDM stimulation.Further study showed that p38αin cDC1s regulated Th2-cell differentiation by modulating the MK2−c-FOS−IL-12 axis.Importantly,crosstalk between p38α-dependent DCs and Th2 cells occurred during the sensitization phase,not the effector phase,and was conserved between mice and humans.Our results identify p38αsignaling as a central pathway in DCs that integrates allergic and parasitic instructive signals with Th2-instructive cytokines from the microenvironment to regulate Th2-cell differentiation and function,and this finding may offer a novel strategy for the treatment of allergic diseases and parasitic infection.

关键词： Allergy p38α dendritic cell Th2

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Laccase/caffeic acid-catalyzed crosslinking coupled with galactomannan alters the conformational structure of OVA and alleviates Th2-mediated allergic asthma

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Food Science and Human Wellness 2023年

作者： Ishfaq Ahmed suidong ouyang Shengquan Wu Haochang Song Miaoyuan Zhang Renxing Luo Peishan Lu Jiaqi Deng Tingting Zheng Yanyan Wang Xinguang Liu Gonghua Huang School of Medical Technology Guangdong Medical University Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics The First Dongguan Affiliated Hospital Guangdong Medical University Haide College Ocean University of China

Ovalbumin (OVA) is the major allergenic protein that can induce T helper 2 (Th2)-allergic reactions for which current treatment options are inadequate. In this study， we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid (Lac/CA)-catalyzed crosslinking in conjunction with galactomannan (Man). The formation of high molecular weight crosslinked polymers and the IgG-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface hydrophobicity. Gastrointestinal digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines (IL-4， IL-5， and IL-13)， and upregulated IFN-γ and IL-10 expression. Stimulation of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers (CD80， and CD86) and MHC class II molecules， and suppressed the expression levels of proinflammatory cytokines. The knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.

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表观遗传修饰调控哮喘发生的研究进展

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生命的化学 2023年第8期43卷 1229-1236页

作者：卢佩珊李佳宁欧阳岁东广东医科大学广东省医学分子诊断重点实验室东莞523808 广东医科大学医学技术学院东莞523808 东莞市寮步医院东莞523430

哮喘是由多种细胞以及细胞组分介导的慢性气道炎症性疾病。其发病率较高、发病时间长且病情反复发作,不容易治愈,已严重影响人们的身体健康。哮喘的发病机制复杂,迄今仍未阐明。近年来,作为一种调控基因变化的方式,表观遗传修饰介导的... 详细信息

哮喘是由多种细胞以及细胞组分介导的慢性气道炎症性疾病。其发病率较高、发病时间长且病情反复发作,不容易治愈,已严重影响人们的身体健康。哮喘的发病机制复杂,迄今仍未阐明。近年来,作为一种调控基因变化的方式,表观遗传修饰介导的基因调控过程与哮喘发病的复杂病理生理变化过程密切相关,是最近被认为影响哮喘发病和异质性的重要机制之一。因此,本文将通过表观遗传修饰的三种主要方式:DNA甲基化、组蛋白修饰和microRNA的异常表达来介绍其在调控哮喘发生中的研究进展,以期为进一步研究哮喘的表观遗传修饰调控机制提供新的思路,以及发现新的哮喘生物标记物和治疗靶点提供参考。

关键词：表观遗传哮喘 DNA甲基化组蛋白修饰 microRNA

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