Abstract
Introduction
Severe burns have long been associated with systemic inflammation and intestinal dysfunction. Recent evidence suggests that intestinal fibrosis may be responsible for intestinal dysfunction after burns. In response to inflammatory stimuli, intestinal epithelial cells may undergo epithelial-mesenchymal transition (EMT). EMT is a process by which epithelial cells acquire a mesenchymal-like phenotype, thereby compromising epithelial barrier function. EMT has been implicated in the pathogenesis of intestinal fibrosis. In the present study, we examined the cellular mechanism of burn-induced intestinal dysfunction.
Methods
Male BALA/c mice (8–12 weeks) received 30% total body surface area full-thickness scald burns or sham procedure. Ileal tissue was collected 5 days after burn for immunofluorescence (IF) and Western blot. Rat intestinal epithelial cell line IEC-6 was treated with cytokines and EMT marker proteins were analyzed by Western blot.
Results
IF data demonstrated that burn significantly increased extracellular matrix (ECM) protein laminin in ileal tissues, suggesting that burn injury induces ileal fibrogenesis. In IEC-6 cells treated with Tumor necrosis factor (TNF) α, IL-1β dose-dependently upregulated α-smooth muscle actin (α-SMA), a well known marker for myofibroblasts. ECM proteins fibronectin and laminin were found to be significantly increased after TNFα treatment. Tight junction protein E-cadherin was decreased after TNFα treatment. Futhermore, TNF receptor signaling antagonist R-7050 and SM7368 blocked TNFα-induced α-SMA upregulation.
Conclusions
Burn-induced mouse ileum ECM upregulation may be through TNFα-mediated EMT.
Applicability of Research to Practice
TNFα receptor antagonism could represent a potential pathway for drug development for treatment of burn-induced intestinal dysfunction.
Characterization and evaluation of lactic acid bacteria candidates for intestinal epithelial permeability and Salmonella Typhimurium colonization in neonatal turkey poults
