Fecal lipocalin2; Potential candidate for a novel biomarker for monitoring colonic inflammation in inflammatory bowel disease

Background: Fecal biomarker has emerged as an important tool for monitoring disease activity in patients with inflammatory bowel disease (IBD). Previous reports showed Lipocalin2 (Lcn2) highly up-regulated in various epithelial cells in response to inflammatory signals. The aim of this study is to evaluate whether fecal Lcn2 is useful as a biomarker for monitoring colonic inflammation using murine experimental colitis model. Methods: 1) Expression of Lcn2 in the colonic tissues of IL-10 knock-out (KO) and control mice (C57BL/6) was evaluated by quantitative real-time PCR and immunohistochemistry. 2) We determined fecal levels of Lcn2 by ELISA, and examined the correlation with histologic colitis score. 3) Secretion of Lcn2 from murine colonic epithelial cell-line, Colon-26, treated with TLR's stimulators and inflammatory cytokines was quantified by ELISA. Result: 1) Increased expression of Lcn2 was observed in the inflamed colonic tissues of IL-10KO mice, whereas rarely determined in control mice. Lcn2 expression was mainly localized in the colonic epithelial cells of IL-10KO mice. 2) Fecal levels of Lcn2 increased time-dependently in IL-10KO mice, and had a significant positive correlation with histologic colitis score. 3) Stimulation with LPS, IL-1β, and IL-17A enhanced Lcn2 secretion from Colon-26 cells. Conclusion: The quantification of fecal Lcn2 could be a promising novel biomarker for monitoring colonic inflammation in IBD.