Expression of T oll‐like receptor‐3 is enhanced in active inflammatory bowel disease and mediates the excessive release of lipocalin 2

Summary 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 ( LCN 2) 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), LCN 2 was localized using immunohistochemistry and in‐situ hybridization. Moreover, we examined the regulation of LCN 2 in HT ‐29 cells with a panel of pattern recognition receptors ( PRR s) and sought evidence by immunohistochemistry that the most relevant PRR , the T oll‐like receptor ( TLR)‐ 3, was indeed expressed in colonic epithelium in IBD . LCN 2 was among the 10 most up‐regulated genes in both active ulcerative colitis ( UC a) and active C rohn's disease ( CD a) versus healthy controls. LCN 2 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 LCN 2 as measured in the gene expression analysis takes place in the mucosal epithelial cells. LCN 2 is a putative biomarker in faeces for intestinal inflammation, different from calprotectin due to its epithelial site of synthesis. LCN 2 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.