Peptide antibiotic human beta-defensin-1 and -2 contribute to antimicrobial defense of the intrahepatic biliary tree
Peptide antibiotic human beta-defensin-1 and -2 contribute to antimicrobial defense of the intrahepatic biliary tree
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DOI：
10.1002/hep.20379
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发表时间：
2004-10-01
期刊：
影响因子：
13.5
通讯作者：
Nakanuma, Y
中科院分区：
文献类型：
--
作者：
Harada, K;Ohba, K;Nakanuma, Y
人β -防御素（hBDs）是重要的抗菌肽，在粘膜表面促进先天免疫。本研究研究了hBD-1和hBD-2在人肝脏标本肝内胆道上皮细胞和4个培养细胞（2个由胆道上皮细胞组成，2个由胆管癌细胞组成）中的表达情况。同时测定胆汁标本中hBD-1和hBD-2的含量。在所有研究的患者中，hBD-1在肝内胆道上皮和肝细胞中非特异性免疫组织化学表达，但在10例肝外胆道梗阻（ebo）患者中有8例，11例肝内胆管结石患者中有7例，6例原发性胆汁性肝硬化（PBC）患者中有1例，5例原发性硬化性胆管炎（PSC）患者中有1例，6例慢性丙型肝炎（CH-C）患者中有0例，11例肝脏组织学正常患者中有0例中，hBD-2的表达仅限于肝内胆管。胆管中hBD-2表达明显，表现为活动性炎症。血清C反应蛋白水平与胆道上皮hBD-2表达相关。实时荧光定量PCR结果显示，在28例新鲜肝脏标本中，包括肝结石患者、PBC、PSC、CH-C和正常肝脏组织标本中，hBD-1信使RNA一致表达，而hBD-2信使RNA在肝结石患者胆道上皮中选择性表达。免疫印迹分析显示，3例PSC患者中有1例，3例PBC患者中有1例，6例肝内结石患者中均有胆汁中有hBD-2蛋白；相比之下，在所有检查的胆汁样本中均可检测到hBD-1。四种培养的胆道上皮细胞系一致表达hBD-1；相反，这些细胞系不能自发表达hBD-2，而是通过大肠杆菌、脂多糖、白细胞介素-1 β或肿瘤坏死因子- α诱导表达hBD-2。总之，这些研究结果表明，在肝内胆道树中，hBD-2在对局部感染和/或活动性炎症的反应中表达，而hBD-1可能构成胆道抗菌防御系统的一个预先存在的组成部分。
Human beta-defensins (hBDs) are important antimicrobial peptides that contribute to innate immunity at mucosal surfaces. This study was undertaken to investigate the expression of hBD-1 and hBD-2 in intrahepatic biliary epithelial cells in specimens of human liver, and 4 cultured cell fines (2 consisting of biliary epithelial cells and 2 cholangiocarcinoma cells). In addition, hBD-1 and hBD-2 were assayed in specimens of bile. hBD-1 was nonspecifically expressed immunohistochemically in intrahepatic biliary epithelium and hepatocytes in all patients studied, but expression of hBD-2 was restricted to large intrahepatic bile ducts in 8 of 10 patients with extrahepatic biliary obstruction OEBO), 7 of 11 with hepatolithiasis, 1 of 6 with primary biliary cirrhosis (PBC), 1 of 5 with primary sclerosing cholangitis (PSC), 0 of 6 with chronic hepatitis C (CH-C), and 0 of 11 with normal hepatic histology. hBD-2 expression was evident in bile ducts exhibiting active inflammation. Serum C reactive protein levels correlated with biliary epithelial expression of hBD-2. Real-time PCR revealed that in all of 28 specimens of fresh liver, including specimens from patients with hepatolithiasis, PBC, PSC, CH-C and normal hepatic histology, hBD-1 messenger RNA was consistently expressed, whereas hBD-2 messenger RNA was selectively expressed in biliary epithelium of patients with hepatolithiasis. Immunobloting analysis revealed hBD-2 protein in bile in 1 of 3 patients with PSC, 1 of 3 with PBC, and each of 6 with hepatolithiasis; in contrast, hBD-1 was detectable in all bile samples examined. Four cultured biliary epithelial cell lines consistently expressed hBD-1; in contrast these cell lines did not express hBD-2 spontaneously but were induced to express hBD-2 by treatment with Eschericia coli, lipopolysaccharide, interleukin-1beta or tumor necrosis factor-alpha. In conclusion, these findings suggest that in the intrahepatic biliary tree, hBD-2 is expressed in response to local infection and/or active inflammation, whereas hBD-1 may constitute a preexisting component of the biliary antimicrobial defense system.