Expression of Toll-like receptor-3 is enhanced in active inflammatory bowel disease and mediates the excessive release of lipocalin 2.
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.
['Østvik|A E|AE|', 'Granlund|A V B|AV|', 'Torp|S H|SH|', 'Flatberg|A|A|', 'Beisvåg|V|V|', 'Waldum|H L|HL|', 'Flo|T H|TH|', 'Espevik|T|T|', 'Damås|J K|JK|', 'Sandvik|A K|AK|']
D000209:Acute-Phase Proteins D000328:Adult D000368:Aged D001706:Biopsy D003093:Colitis, Ulcerative D003424:Crohn Disease D005260:Female D005786:Gene Expression Regulation D020868:Gene Silencing D019073:HT29 Cells D006801:Humans D015212:Inflammatory Bowel Diseases D007413:Intestinal Mucosa D000071068:Lipocalin-2 D054834:Lipocalins D008297:Male D008875:Middle Aged D011070:Poly I-C D021381:Protein Transport D011518:Proto-Oncogene Proteins D012333:RNA, Messenger D051196:Toll-Like Receptor 3 D055815:Young Adult
inflammatory bowel disease lipocalin 2 ulcerative colitis Crohn's disease TLR-3