Davies Darren, Meade Kieran G, Herath Shan, Eckersall P David, Gonzalez Deyarina, White John O, Conlan R Steven, O'Farrelly Cliona, Sheldon I Martin
Department of Veterinary Clinical Sciences, Royal Veterinary College, Royal College Street, London, UK.
Reprod Biol Endocrinol. 2008 Nov 18;6:53. doi: 10.1186/1477-7827-6-53.
The endometrium is commonly infected with bacteria leading to severe disease of the uterus in cattle and humans. The endometrial epithelium is the first line of defence for this mucosal surface against bacteria and Toll-like receptors (TLRs) are a critical component of the innate immune system for detection of pathogen associated molecular patterns (PAMPs). Antimicrobial peptides, acute phase proteins and Mucin-1 (MUC-1) also provide non-specific defences against microbes on mucosal surfaces. The present study examined the expression of innate immune defences in the bovine endometrium and tested the hypothesis that endometrial epithelial cells express functional receptors of the TLR family and the non-specific effector molecules for defence against bacteria.
Bovine endometrial tissue and purified populations of primary epithelial and stromal cells were examined using RT-PCR for gene expression of TLRs, antimicrobial peptides and MUC-1. Functional responses were tested by evaluating the secretion of prostaglandin E(2) and acute phase proteins when cells were treated with bacterial PAMPs such as bacterial lipopolysaccharide (LPS) and lipoproteins.
The endometrium expressed TLRs 1 to 10, whilst purified populations of epithelial cells expressed TLRs 1 to 7 and 9, and stromal cells expressed TLRs 1 to 4, 6, 7, 9 and 10. The TLRs appear to be functional as epithelial cells secreted prostaglandin E(2) in response to bacterial PAMPs. In addition, the epithelial cells expressed antimicrobial peptides, such as Tracheal and Lingual Antimicrobial Peptides (TAP and LAP) and MUC-1, which were upregulated when the cells were treated with LPS. However, the epithelial cells did not express appreciable amounts of the acute phase proteins haptoglobin or serum amyloid A.
Epithelial cells have an essential role in the orchestration of innate immune defence of the bovine endometrium and are likely to be the key to prevention of endometrial infection with bacteria.
子宫内膜常被细菌感染,从而导致牛和人类的严重子宫疾病。子宫内膜上皮是该黏膜表面抵御细菌的第一道防线,而 Toll 样受体(TLRs)是天然免疫系统中检测病原体相关分子模式(PAMPs)的关键组成部分。抗菌肽、急性期蛋白和黏蛋白 -1(MUC -1)也为黏膜表面抵御微生物提供非特异性防御。本研究检测了牛子宫内膜中天然免疫防御的表达情况,并验证了子宫内膜上皮细胞表达 TLR 家族功能性受体以及抵御细菌的非特异性效应分子这一假设。
使用逆转录聚合酶链反应(RT-PCR)检测牛子宫内膜组织以及纯化的原代上皮细胞和基质细胞群体中 TLRs、抗菌肽和 MUC -1 的基因表达。当细胞用细菌脂多糖(LPS)和脂蛋白等细菌 PAMPs 处理时,通过评估前列腺素 E2 和急性期蛋白的分泌来测试功能反应。
子宫内膜表达 TLRs 1 至 10,而纯化的上皮细胞群体表达 TLRs 1 至 7 和 9,基质细胞表达 TLRs 1 至 4、6、7、9 和 10。这些 TLRs 似乎具有功能,因为上皮细胞会响应细菌 PAMPs 分泌前列腺素 E2。此外,上皮细胞表达抗菌肽,如气管和舌抗菌肽(TAP 和 LAP)以及 MUC -1,在用 LPS 处理细胞时这些物质会上调。然而,上皮细胞未表达可观量的急性期蛋白触珠蛋白或血清淀粉样蛋白 A。
上皮细胞在牛子宫内膜天然免疫防御的协调中起重要作用,很可能是预防子宫内膜细菌感染的关键。