杭州浙大迪迅生物基因工程有限公司Allergy：Der p 13是脂肪酸结合蛋白和天然免疫应答催化剂
发布日期：2018-11-26
原标题：小屋尘螨变应原Der p 13是一种脂肪酸结合蛋白并且是TLR2介导免疫应答的催化剂
延伸阅读
Allergy
DOI: :10.1111/all.12899
Abstract:
Background: The house dust mite (HDM) allergen Der p 13 could be a lipid-binding protein able to activate key innate signaling pathways in the initiation of the allergic response. We investigated the IgE reactivity of recombinant Der p 13 (rDer p 13), its lipid-binding activities, and its capacity to stimulate airway epithelium cells.
Methods: Purified rDer p 13 was characterized by mass spectrometry, circular dichroism, fluorescence-based lipid-binding assays, and in silico structural prediction. IgE-binding activity and allergenic potential of Der p 13 were examined by ELISA,basophil degranulation assays, and in vitro airway epithelial cell activation assays.
Results: Protein modeling and biophysical analysis indicated that Der p 13 adopts a b-barrel structure with a predominately apolar pocket representing a potential binding site for hydrophobic ligands. Fluorescent lipid-binding assays confirmed that the protein is highly selective for ligands and that it binds a fatty acid with a dissociation constant typical of lipid transporter proteins. The low IgE-binding frequency (7%, n = 224) in Thai HDM-allergic patients as well as the limited propensity to activate basophil degranulation classifies Der p 13 as a minor HDM allergen. Nevertheless, the protein with its presumptively associated lipid(s) triggered the production of IL-8 and GM-CSF in respiratory epithelial cells through a TLR2-, MyD88-, NF-kB-, and MAPK-dependent signaling pathway.
Conclusions: Although a minor allergen, Der p 13 may, through its lipid-binding capacity, play a role in the initiation of the HDM-allergic response through TLR2 activation.
First Author:
P. Satitsuksanoa
Correspondence:
Assoc. Prof. Dr. Alain Jacquet, Department of Medicine, Faculty of Medicine, Chulalongkorn University
All Authors:
P. Satitsuksanoa, M. Kennedy, D. Gilis, M. Le Mignon, N. Suratannon, W. T. Soh, J. Wongpiyabovorn, P. Chatchatee, M. Vangveravong, T. Rerkpattanapipat, A. Sangasapaviliya, S. Piboonpocanun, E.
——来自浙大迪迅
① 屋尘螨（HDM）变应原Der p 13可能是一种脂结合蛋白，能够激活启动变应反应的关键先天信号通路；② 纯化的rDer p 13通过质谱、圆二色性、基于荧光的脂质结合分析和硅结构预测等方法来进行表征分析；③ 采用ELISA、嗜碱性粒细胞脱颗粒试验和体外气道上皮细胞活化试验检测Der p 13的IgE结合活性和致敏活性；④ 荧光脂质结合试验证实，该蛋白质对配体具有高度选择性，并且它与脂肪酸结合具有典型的脂质转运蛋白解离常数；⑤ Der p 13 通过其脂质结合能力，并由TLR2激活，然后在HDM过敏反应中起作用。
延伸阅读
Allergy
[IF:6.048]
The minor house dust mite allergen Der p 13 is a fatty acid-binding protein and an activator of a TLR2-mediated innate immune responseDOI: :10.1111/all.12899
Abstract:
Background: The house dust mite (HDM) allergen Der p 13 could be a lipid-binding protein able to activate key innate signaling pathways in the initiation of the allergic response. We investigated the IgE reactivity of recombinant Der p 13 (rDer p 13), its lipid-binding activities, and its capacity to stimulate airway epithelium cells.
Methods: Purified rDer p 13 was characterized by mass spectrometry, circular dichroism, fluorescence-based lipid-binding assays, and in silico structural prediction. IgE-binding activity and allergenic potential of Der p 13 were examined by ELISA,basophil degranulation assays, and in vitro airway epithelial cell activation assays.
Results: Protein modeling and biophysical analysis indicated that Der p 13 adopts a b-barrel structure with a predominately apolar pocket representing a potential binding site for hydrophobic ligands. Fluorescent lipid-binding assays confirmed that the protein is highly selective for ligands and that it binds a fatty acid with a dissociation constant typical of lipid transporter proteins. The low IgE-binding frequency (7%, n = 224) in Thai HDM-allergic patients as well as the limited propensity to activate basophil degranulation classifies Der p 13 as a minor HDM allergen. Nevertheless, the protein with its presumptively associated lipid(s) triggered the production of IL-8 and GM-CSF in respiratory epithelial cells through a TLR2-, MyD88-, NF-kB-, and MAPK-dependent signaling pathway.
Conclusions: Although a minor allergen, Der p 13 may, through its lipid-binding capacity, play a role in the initiation of the HDM-allergic response through TLR2 activation.
First Author:
P. Satitsuksanoa
Correspondence:
Assoc. Prof. Dr. Alain Jacquet, Department of Medicine, Faculty of Medicine, Chulalongkorn University
All Authors:
P. Satitsuksanoa, M. Kennedy, D. Gilis, M. Le Mignon, N. Suratannon, W. T. Soh, J. Wongpiyabovorn, P. Chatchatee, M. Vangveravong, T. Rerkpattanapipat, A. Sangasapaviliya, S. Piboonpocanun, E.
2018-11-06 Article
创建过敏性疾病的科研、科普知识交流平台，为过敏患者提供专业诊断、治疗、预防的共享平台。
