The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure Export

@article{citeulike:5840782, abstract = {BACKGROUND:Spontaneous bacterial peritonitis (SBP) is a common clinical disease and one of the more severe complications of acute liver failure (ALF). Although the mechanism responsible for SBP is unclear, cytokines play an important role. The aim of this study was to investigate the effects of tumor necrosisfactor-alpha (TNF-alpha) on the structure of the intestinal mucosa and the expression of tight junction (zona occludens 1; ZO-1) protein in a mouse model of ALF. METHODS:We induced ALF using D-galactosamine / lipopolysaccharide (GalN/LPS) or GalN/TNF-alpha and assessed the results using transmission electron microscopy, immunohistochemistry, Western blotting, semi-quantitative reverse transcriptase PCR, and real-time quantitative PCR. The effects of administration of anti-TNF-alpha IgG antibody or anti-TNF-alpha R1 antibody before administration of GalN/LPS or GalN/TNF-alpha, respectively, on TNF-alpha were also assessed. RESULTS:Morphological abnormalities in the intestinal mucosa of ALF mice were positively correlated with serum TNF-alpha level. Electron microscopic analysis revealed tight junction (TJ) disruptions, epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was significantly decreased in both ALF models, as was the level of ZO-1 protein. Prophylactic treatment with either anti-TNF-alpha IgG antibody or anti-tumor necrosis factor-a receptor 1(anti-TNF-alpha R1) antibody prevented changes in intestinal tissue ultrastructure and ZO-1 expression. CONCLUSIONS:TNF-alpha affects the structure of the intestinal mucosa, decreases expression of ZO-1, and affects the morphology of the colon in a mouse model of ALF. It also may participate in the pathophysiological mechanism of SBP complicated to ALF.}, author = {Song, Hongli and Lv, Sa and Liu, Pei}, citeulike-article-id = {5840782}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1471-230X-9-70}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19772664}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19772664}, day = {22}, doi = {10.1186/1471-230X-9-70}, issn = {1471-230X}, journal = {BMC Gastroenterology}, keywords = {tnf-a}, month = {September}, number = {1}, pages = {70+}, posted-at = {2009-09-29 02:40:15}, priority = {3}, title = {The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure}, url = {http://dx.doi.org/10.1186/1471-230X-9-70}, volume = {9}, year = {2009} }

TY - JOUR ID - citeulike:5840782 L3 - citeulike-article-id:5840782 N2 - BACKGROUND:Spontaneous bacterial peritonitis (SBP) is a common clinical disease and one of the more severe complications of acute liver failure (ALF). Although the mechanism responsible for SBP is unclear, cytokines play an important role. The aim of this study was to investigate the effects of tumor necrosisfactor-alpha (TNF-alpha) on the structure of the intestinal mucosa and the expression of tight junction (zona occludens 1; ZO-1) protein in a mouse model of ALF. METHODS:We induced ALF using D-galactosamine / lipopolysaccharide (GalN/LPS) or GalN/TNF-alpha and assessed the results using transmission electron microscopy, immunohistochemistry, Western blotting, semi-quantitative reverse transcriptase PCR, and real-time quantitative PCR. The effects of administration of anti-TNF-alpha IgG antibody or anti-TNF-alpha R1 antibody before administration of GalN/LPS or GalN/TNF-alpha, respectively, on TNF-alpha were also assessed. RESULTS:Morphological abnormalities in the intestinal mucosa of ALF mice were positively correlated with serum TNF-alpha level. Electron microscopic analysis revealed tight junction (TJ) disruptions, epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was significantly decreased in both ALF models, as was the level of ZO-1 protein. Prophylactic treatment with either anti-TNF-alpha IgG antibody or anti-tumor necrosis factor-a receptor 1(anti-TNF-alpha R1) antibody prevented changes in intestinal tissue ultrastructure and ZO-1 expression. CONCLUSIONS:TNF-alpha affects the structure of the intestinal mucosa, decreases expression of ZO-1, and affects the morphology of the colon in a mouse model of ALF. It also may participate in the pathophysiological mechanism of SBP complicated to ALF. IS - 1 JF - BMC Gastroenterology SN - 1471-230X TI - The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure VL - 9 SP - 70 KW - tnf-a AU - Song, Hongli AU - Lv, Sa AU - Liu, Pei PY - 2009/09/22/ UR - http://dx.doi.org/10.1186/1471-230X-9-70 ER -