Treatment with glutamine is associated with down-regulation of Toll-like receptor-4 and myeloid differentiation factor 88 expression and decrease in intestinal mucosal injury caused by lipopolysaccharide endotoxaemia in a rat
Kessel, A.; Toubi, E.; Pavlotzky, E.; Mogilner, Jorge G.; Coran, A. G.; Lurie, Michael; Karry, R.; Sukhotnik, Igor
2008-02
Citation
Kessel, A.; Toubi, E.; Pavlotzky, E.; Mogilner, J.; Coran, A. G.; Lurie, M.; Karry, R.; Sukhotnik, I. (2008). "Treatment with glutamine is associated with down-regulation of Toll-like receptor-4 and myeloid differentiation factor 88 expression and decrease in intestinal mucosal injury caused by lipopolysaccharide endotoxaemia in a rat." Clinical & Experimental Immunology 151(2): 341-347. <http://hdl.handle.net/2027.42/73475>
Abstract
Recent evidence suggests that lipopolysaccharide (LPS) endotoxaemia in a rat causes significant mucosal injury. Our objective was to determine the effects of glutamine (Gln) on Toll-like receptor 4 (TLR-4), myeloid differentiation factor 88 (Myd88) and tumour necrosis factor (TNF)-α receptor-associated factor 6 (TRAF6) expression in intestinal mucosa following LPS endotoxaemia in a rat. For this purpose, male Sprague–Dawley rats were assigned randomly to one of three experimental groups of 10 rats each: (i) control rats underwent intraperitoneal (i.p.) injection of sterile saline once a day; (ii) rats were treated with LPS given i.p. once a day at a dose of 10 mg/kg for 48 h (two doses); and (iii) rats were pretreated with oral Gln given in drinking water (2%) 48 h before and following injection of LPS. Intestinal mucosal parameters, enterocyte proliferation and apoptosis were determined at death. TLR-4 and MyD88 mRNA expression was measured with reverse transcription–polymerase chain reaction (RT–PCR). TLR-4 and MyD88 protein expression were analysed by Western immunoblotting. We observed a statistically significant ( P < 0·05) decrease in mucosal weight, mucosal DNA and enterocyte proliferation and a significant increase in enterocyte apoptosis in rat intestine, following LPS administration. These changes were attenuated significantly by dietary Gln. Expression of TLR-4, MyD88 and TRAF6 mRNA in the mucosal ileum was significantly higher in LPS rats versus control rats ( P = 0·0006, P = 0·0015, P = 0·03, respectively) as well as TLR-4 and MyD88 protein expression. The administration of Gln reduced significantly the expression of TLR-4, MyD88 and TRAF6 ( P = 0·023, P = 0·014, P = 0·035, respectively) mRNA as well as TLR-4 and MyD88 protein expression in ileum compared to LPS animals. We did not find a significant change in the expression of TLR-4, MyD88 or TRAF6 in the jejunum of different groups. We conclude that treatment with Gln was associated with down-regulation of TLR-4, MyD88 and TRAF6 expression and concomitant decrease in intestinal mucosal injury caused by LPS endotoxaemia in a rat.Publisher
Blackwell Publishing Ltd
ISSN
0009-9104 1365-2249
Other DOIs
PMID
18070149
Types
Article
URI
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18070149&dopt=citationMetadata
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