Sang Yongming, Ramanathan Balaji, Ross Christopher R, Blecha Frank
Department of Anatomy and Physiology, College of Veterinary Medicine, 228 Coles Hall, Kansas State University, Manhattan, KS 66506-5802, USA.
Infect Immun. 2005 Nov;73(11):7133-41. doi: 10.1128/IAI.73.11.7133-7141.2005.
Peptidoglycan recognition proteins (PGRPs) are a group of newly identified proteins with emerging functions in mammalian innate immunity. Here we report the identification and characterization of two long isoforms of porcine PGRP. Their complete cDNA sequences encode predicted peptides of 252 and 598 residues and are named pPGRP-L1 and pPGRP-L2, respectively. These porcine isoforms share identical PGRP domains at their C terminus, which are highly conserved with human and mouse orthologs. pPGRP-L1 is expressed constitutively in several tissues, including bone marrow, intestine, liver, spleen, kidney, and skin. pPGRP-L2 is highly expressed in the duodenum and liver, and expression in intestinal tissues is increased by Salmonella infection. In intestinal cells, expression of both pPGRP-L1 and pPGRP-L2 is increased by bacterial infection. Recombinant pPGRP-L1 and pPGRP-L2 have N-acetylmuramoyl-L-alanine amidase activity. Loss-of-function and gain-of-function experiments indicate that these two pPGRPs are involved in expression of the antimicrobial peptide beta-defensin-1. Silencing of pPGRP-L2 in intestinal cells challenged with Listeria monocytogenes results in downregulation of beta-defensin-1. Conversely, overexpression of pPGRP-L1 or pPGRP-L2 dramatically upregulates expression of beta-defensin-1. Collectively, these findings suggest that porcine PGRPs are involved in antimicrobial peptide expression.
肽聚糖识别蛋白（PGRPs）是一组新发现的蛋白，在哺乳动物先天免疫中发挥着越来越重要的作用。在此，我们报告了猪PGRP两种长亚型的鉴定和特征。它们完整的cDNA序列编码预测的分别含252和598个残基的肽段，分别命名为pPGRP-L1和pPGRP-L2。这些猪亚型在其C末端具有相同的PGRP结构域，与人及小鼠的直系同源物高度保守。pPGRP-L1在包括骨髓、肠道、肝脏、脾脏、肾脏和皮肤在内的多种组织中组成性表达。pPGRP-L2在十二指肠和肝脏中高表达，沙门氏菌感染会增加其在肠道组织中的表达。在肠道细胞中，细菌感染会增加pPGRP-L1和pPGRP-L2的表达。重组pPGRP-L1和pPGRP-L2具有N-乙酰胞壁酰-L-丙氨酸酰胺酶活性。功能丧失和功能获得实验表明，这两种pPGRPs参与抗菌肽β-防御素-1的表达。在单核细胞增生李斯特菌攻击的肠道细胞中沉默pPGRP-L2会导致β-防御素-1的表达下调。相反，pPGRP-L1或pPGRP-L2的过表达会显著上调β-防御素-1的表达。总体而言，这些发现表明猪PGRPs参与抗菌肽的表达。
