九肽激活肥大细胞致类过敏反应的作用及其机制

R965; 目的 探讨九肽IVQKIKHCF激活肥大细胞引发类过敏反应的作用及潜在机制.方法 以人肥大细胞系LAD2为对象,以P物质为阳性对照,通过检测β-氨基己糖苷酶释放率、组胺释放量、炎症因子释放量来考察25、50、100 μmol/L IVQKIKHCF的激活作用;分别以敲低MrgprX2的LAD2细胞和Mas相关G蛋白偶联受体X2(MRGPRX2)高表达的人胚胎肾细胞系HEK293(MRGPRX2/HEK293细胞)为对象,通过检测β-氨基己糖苷酶释放率和细胞内钙离子浓度来评价IVQKIKHCF激活作用与MRGPRX2的相关性.结果 25、50、100 μmol/L的IVQKIKHCF...

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Published in中国药房 Vol. 34; no. 24; pp. 2995 - 2999
Main Authors 陈晓敏, 刘娜, 张丽娜, 李友佳
Format Journal Article
LanguageChinese
Published 西安交通大学第二附属医院药学部,西安 710004 01.12.2023
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ISSN1001-0408
DOI10.6039/j.issn.1001-0408.2023.24.07

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Abstract R965; 目的 探讨九肽IVQKIKHCF激活肥大细胞引发类过敏反应的作用及潜在机制.方法 以人肥大细胞系LAD2为对象,以P物质为阳性对照,通过检测β-氨基己糖苷酶释放率、组胺释放量、炎症因子释放量来考察25、50、100 μmol/L IVQKIKHCF的激活作用;分别以敲低MrgprX2的LAD2细胞和Mas相关G蛋白偶联受体X2(MRGPRX2)高表达的人胚胎肾细胞系HEK293(MRGPRX2/HEK293细胞)为对象,通过检测β-氨基己糖苷酶释放率和细胞内钙离子浓度来评价IVQKIKHCF激活作用与MRGPRX2的相关性.结果 25、50、100 μmol/L的IVQKIKHCF可显著提高LAD2细胞的β-氨基己糖苷酶释放率和组胺释放量(P<0.05),并不同程度地促进肿瘤坏死因子α、白细胞介素8、巨噬细胞炎症蛋白1β、单核细胞趋化蛋白1的释放(P<0.05);敲低MrgprX2后,25、50、100 μmol/L的IVQKIKHCF对LAD2细胞β-氨基己糖苷酶释放的促进作用被显著逆转(P<0.05),且可升高MRGPRX2/HEK293细胞内的钙离子浓度.结论 九肽IVQKIKHCF可通过激活MRGPRX2而促进肥大细胞释放颗粒物质和炎症介质,从而引发类过敏反应.
AbstractList R965; 目的 探讨九肽IVQKIKHCF激活肥大细胞引发类过敏反应的作用及潜在机制.方法 以人肥大细胞系LAD2为对象,以P物质为阳性对照,通过检测β-氨基己糖苷酶释放率、组胺释放量、炎症因子释放量来考察25、50、100 μmol/L IVQKIKHCF的激活作用;分别以敲低MrgprX2的LAD2细胞和Mas相关G蛋白偶联受体X2(MRGPRX2)高表达的人胚胎肾细胞系HEK293(MRGPRX2/HEK293细胞)为对象,通过检测β-氨基己糖苷酶释放率和细胞内钙离子浓度来评价IVQKIKHCF激活作用与MRGPRX2的相关性.结果 25、50、100 μmol/L的IVQKIKHCF可显著提高LAD2细胞的β-氨基己糖苷酶释放率和组胺释放量(P<0.05),并不同程度地促进肿瘤坏死因子α、白细胞介素8、巨噬细胞炎症蛋白1β、单核细胞趋化蛋白1的释放(P<0.05);敲低MrgprX2后,25、50、100 μmol/L的IVQKIKHCF对LAD2细胞β-氨基己糖苷酶释放的促进作用被显著逆转(P<0.05),且可升高MRGPRX2/HEK293细胞内的钙离子浓度.结论 九肽IVQKIKHCF可通过激活MRGPRX2而促进肥大细胞释放颗粒物质和炎症介质,从而引发类过敏反应.
Abstract_FL OBJECTIVE To study the effects and potential mechanism of anaphylactoid reaction induced by nonapeptide IVQKIKHCF activating mast cells.METHODS Using human mast cell line LAD2 as subject,and substance P as positive control,the activation effects of 25,50 and 100 μmol/L IVQKIKHCF on mast cells were investigated by determining the release rate of β-aminohexosidase,histamine release,and the contents of inflammatory factors;using MrgprX2-knockdown LAD2 cells and Mas-related G protein-coupled receptor X2(MRGPRX2)high-expression human embryonic kidney cell line HEK293(MRGPRX2/HEK293 cells)as subject,the correlation between the activation effect of IVQKIKHCF and MRGPRX2 was investigated by determining the release rate of β-aminohexosidase,and intracellular calcium ion concentration.RESULTS IVQKIKHCF with 25,50,100 μmol/L could significantly increase the release rate of β-aminohexosidase and histamine release in LAD2 cells(P<0.05),and promote the release of tumor necrosis factor-α,interleukin-8,macrophage inflammatory protein-1β and monocyte chemotactic protein-1 to varying degrees(P<0.05).After knocking down MrgprX2,the effects of 25,50,100 μmol/L IVQKIKHCF promoting the release of β-aminohexosidase in LAD2 cells were reversed significantly(P<0.05),resulting in an increase of calcium ion concentration in MRGPRX2/HEK293 cells.CONCLUSIONS Nonapeptide IVQKIKHCF can promote mast cells to release granular matter and inflammatory mediators by activating MRGPRX2 thus inducing anaphylactoid reaction.
Author 李友佳
张丽娜
陈晓敏
刘娜
AuthorAffiliation 西安交通大学第二附属医院药学部,西安 710004
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Author_FL CHEN Xiaomin
ZHANG Lina
LI Youjia
LIU Na
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Keywords 类过敏反应
Mas-related G protein-coupled receptor X2
肥大细胞
IVQKIKHCF
nonapeptide
mast cell
九肽
Mas相关G蛋白偶联受体X2
anaphylactoid reaction
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Title 九肽激活肥大细胞致类过敏反应的作用及其机制
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