Centre of Molecular Inflammation Research, Department of Cancer Research, Norwegian University of Science and Technology, Trondheim, Norway.
Clin Exp Immunol. 2013 Sep;173(3):502-11. doi: 10.1111/cei.12136.
Anti-microbial peptides might influence the pathogenesis and course of inflammatory bowel disease (IBD). We sought to clarify the role of the anti-microbial glycoprotein lipocalin 2 (LCN2) in the colon by determining its localization and regulation in IBD. Following a microarray gene expression study of colonic biopsies from a large IBD population (n = 133), LCN2 was localized using immunohistochemistry and in-situ hybridization. Moreover, we examined the regulation of LCN2 in HT-29 cells with a panel of pattern recognition receptors (PRRs) and sought evidence by immunohistochemistry that the most relevant PRR, the Toll-like receptor (TLR)-3, was indeed expressed in colonic epithelium in IBD. LCN2 was among the 10 most up-regulated genes in both active ulcerative colitis (UCa) and active Crohn's disease (CDa) versus healthy controls. LCN2 protein was found in both epithelial cells and infiltrating neutrophils, while mRNA synthesis was located solely to epithelial cells, indicating that de-novo synthesis and thus regulation of LCN2 as measured in the gene expression analysis takes place in the mucosal epithelial cells. LCN2 is a putative biomarker in faeces for intestinal inflammation, different from calprotectin due to its epithelial site of synthesis. LCN2 release from the colonic epithelial cell line HT-29 was enhanced by both interleukin (IL)-1β and the TLR-3 ligand poly(I:C), and TLR-3 was shown to be expressed constitutively in colonic epithelial cells and markedly increased during inflammation.
抗菌肽可能影响炎症性肠病 (IBD) 的发病机制和病程。我们试图通过确定抗菌糖蛋白 lipocalin 2 (LCN2) 在 IBD 中的定位和调节来阐明其在结肠中的作用。在对来自大型 IBD 人群（n=133）的结肠活检进行了微阵列基因表达研究后，我们使用免疫组织化学和原位杂交技术确定了 LCN2 的定位。此外，我们用一组模式识别受体 (PRR) 检查了 HT-29 细胞中 LCN2 的调节，并通过免疫组织化学检查了最相关的 PRR，即 Toll 样受体 (TLR)-3，实际上在 IBD 中表达于结肠上皮细胞。LCN2 是活动性溃疡性结肠炎 (UCa) 和活动性克罗恩病 (CDa) 与健康对照组相比上调最明显的 10 个基因之一。LCN2 蛋白存在于上皮细胞和浸润的中性粒细胞中，而 mRNA 合成仅位于上皮细胞，表明 LCN2 的从头合成和因此在基因表达分析中测量的调节发生在粘膜上皮细胞中。LCN2 是粪便中肠道炎症的一种潜在生物标志物，与 calprotectin 不同，因为它的合成部位在肠上皮细胞。IL-1β 和 TLR-3 配体 poly(I:C) 增强结肠上皮细胞系 HT-29 释放 LCN2，并且 TLR-3 在结肠上皮细胞中持续表达，并在炎症期间显著增加。
