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Characterization of host defense molecules in the human pancreas

机译:人体胰腺中宿主防病的特征

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The gut microbiota can play a role in pancreatitis and, likely, in the development of type 1 diabetes (T1D). Anti-microbial peptides and secretory proteins are important mediators of the innate immune response against bacteria but their expression in the human pancreas is not fully known. In this study, immunohistochemistry was used to analyze the expression of seven antimicrobial peptides (Defensin alpha1, alpha4, beta1-4 and Cathelicidin) and two secretory proteins with known antimicrobial properties (REG3A and GP2) in pancreatic and duodenal biopsies from 10 non-diabetic organ donors and one organ donor that died at onset of T1D. Immunohistochemical data was compared with previously published whole-transcriptome data sets. Seven (Defensin alpha1, beta2, beta3, alpha4, GP2, Cathelicidin, and REG3A) host defense molecules showed positive staining patterns in most non-diabetic organ donors, whereas two (Defensin beta1 and beta4) were negative in all non-diabetic donors. Two molecules (Defensin a1 and GP2) were restricted to the exocrine pancreas whereas two (Defensin beta3, alpha4) were only expressed in islet tissue. Cathelicidin, beta2, and REG3A were expressed in both islets and exocrine tissue. The donor that died at onset of T1D had generally less positivity for the host defense molecules, but, notably, this pancreas was the only one where defensin beta1 was found. Neither donor age, immune-cell infiltration, nor duodenal expression correlated to the pancreatic expression of host defense molecules. In conclusion, these findings could have important implications for the inflammatory processes in diabetes and pancreatitis as we find several host defense molecules expressed by the pancreatic tissue.
机译:肠道微生物群可以在胰腺炎中发挥作用,并且可能在1型糖尿病(T1D)的发育中。抗微生物肽和分泌蛋白是对细菌的先天免疫应答的重要介质,但它们在人胰腺中的表达不完全已知。在该研究中,使用免疫组织化学分析七种抗菌肽(Defensin Alpha1,Alpha4,Beta1-4和Cathelicin)的表达,以及来自10个非糖尿病的胰腺和十二指肠活组织检查中已知的抗微生物性质(Reg3a和Gp2)的两个分泌蛋白器官供体和一个在T1D发作时死亡的器官供体。将免疫组化数据与先前公布的全转录组数据集进行了比较。七(Defensin alpha1,Beta2,Beta3,α4,GP2,Cathelicidin和Reg3a)宿主防病在大多数非糖尿病器官供体中显示出阳性染色模式,而两个(Defensin Beta1和Beta4)在所有非糖尿病供体中是阴性的。两个分子(Defensin A1和GP2)限于外分胰腺,而两种(Defensin Beta3,α4)仅在胰岛组织中表达。 Cathelicindin,Beta2和Reg3a在胰岛和外泌体组织中表达。在T1D发作时死亡的供体通常对宿主防御分子的阳性较小,但值得注意的是,这种胰腺是未发现防御β1的唯一胰腺。既不是供体年龄,免疫细胞浸润,也不是与宿主防御分子的胰腺表达相关的十二指肠表达。总之,这些发现可能对糖尿病和胰腺炎的炎症过程具有重要意义,因为我们发现由胰腺组织表达的几个宿主防御分子。

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