Expression and functional analyses of liver expressed antimicrobial peptide-2 (LEAP-2) variant forms in human tissues

Expression and functional analyses of liver expressed antimicrobial peptide-2 (LEAP-2) variant forms in human tissues
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DOI:
10.1016/j.cellimm.2009.11.010
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发表时间:
2010-01-01
影响因子:
4.3
通讯作者:
Hall, Judith
Hall, Judith
中科院分区:
医学4区
文献类型:
--
作者:
Howard, Alison;Townes, Claire;Hall, Judith

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抗微生物肽肝脏表达的抗微生物肽-2(LEAP-2)被认为是脊椎动物先天免疫系统的一部分。然而,LEAP-2肽一级结构在脊椎动物中的高度保守性暗示了更基本的生理作用。RT-PCR分析证实LEAP-2 mRNA变体在人胃肠道(GI)上皮组织和THP-1单核细胞中表达。观察到指示至少三种不同剪接转录物的三种cDNA产物。cDNA序列的翻译支持编码分泌的LEAP-2肽和两种缺乏信号序列的变体的转录本的合成,表明细胞内定位。LEAP-2肽在上皮细胞中的合成和细胞质定位得到免疫组织化学分析的支持。功能数据表明,LEAP-2不参与胃肠道上皮细胞对铁的生理反应,也不是上皮细胞的有丝分裂原或THP-1单核细胞的趋化性。然而,与用脂多糖(100 ng/ml)攻击THP-1单核细胞相关的LEAP-2转录物模式的变化支持肽在先天免疫应答中具有多种作用。(C)2009 Elsevier Inc.所有战斗保留。
The antimicrobial peptide Liver Expressed Antimicrobial Peptide-2 (LEAP-2) is proposed to function as part of the vertebrate innate immune system. However, the highly conserved nature of the LEAP-2 peptide primary structure among vertebrates Suggests more fundamental physiological roles. RT-PCR analyses confirmed expression of LEAP-2 mRNA variants in human gastro-intestinal (GI) epithelial tissues and THP-1 monocytes. Three cDNA products indicative of at least three different spliced transcripts were observed. Translation of the cDNA sequences supported synthesis of transcripts encoding the secreted LEAP-2 peptide and two variants lacking signal sequences Suggesting intracellular localisation. The synthesis and cytoplasmic localisation of LEAP-2 peptides in epithelia Was Supported by immunohistochemical analyses. Functional data Suggested that LEAP-2 is not involved in the physiological response of GI epithelia to iron, nor is it mitogenic for epithelial cells or chemotactic for THP-1 monocytes. However, changes in the LEAP-2 transcript patterns associated with the challenge of THP-1 monocytes with lipopolysaccharide (100 ng/ml) were supportive of the peptides having multiple roles in the innate immune response. (C) 2009 Elsevier Inc. All Fights reserved.