Netrin-1 regulate colon-kidney cross-talk through suppression of IL-6 function in a mouse model of DSS-colitis.

Netrin-1 regulate colon-kidney cross-talk through suppression of IL-6 function in a mouse model of DSS-colitis. Am J Physiol Renal Physiol. 2013 Feb 27; Authors: Ranganathan P, Jayakumar C, Santhakumar M, Ramesh G Abstract Organ cross-talk is increasingly appreciated in human disease, and inflammatory mediators are shown to mediate distant organ injury in many disease models. Colitis and intestinal injury are known to be mediated by infiltrating immune cells and their secreted cytokines. However, its effect on other organs such as kidney has never been studied. In the current study, we examined the effect DSS colitis on kidney injury and inflammation. In addition, we hypothesized that netrin-1 could modulate colon-kidney cross talk through regulation of inflammation and apoptosis. Consistent with our hypothesis, dextran sulfate sodium (DSS)-colitis induced acute kidney injury in mice. Epithelial specific overexpression of netrin-1 suppressed both colitis and colitis induced acute kidney injury which was associated with reduced weight loss, neutrophil infiltration into colon mucosa, intestinal permeability, epithelial cells apoptosis and cytokines and chemokines production in netrin-1 transgenic mice colon and kidney. To determine, whether netrin-1 protective effects were mediated through suppression of IL-6, IL-6 knockout mice were treated with DSS and acute kidney injury was determined. IL-6 knockout was resistant to colitis and acute kidney ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research