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Am J Physiol Gastrointest Liver Physiol (March 13, 2003). doi:10.1152/ajpgi.00307.2002
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Submitted on July 26, 2002
Accepted on March 7, 2003

Amelioration of dextran sulphate colitis by butyrate; role of heat shock protein 70 and nuclear factor kappa B

Aparna Venkatraman1, BS Ramakrishna1*, RV Shaji1, NS Nanda Kumar1, Anna Pulimood1, and Susama Patra1

1 Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore, Tamilnadu, India

* To whom correspondence should be addressed. E-mail: rama{at}cmcvellore.ac.in.

Butyrate enemas have been demonstrated to ameliorate inflammation in ulcerative colitis. The mechanism of this protective effect of butyrate is not known, and this study examines the effect of butyrate on epithelial function, inducible heat shock protein 70 (HSP70) expression, and nuclear factor kappa B (NF-{kappa}B) activation in experimental colitis. Colitis was induced in rats by oral dextran sulphate sodium (DSS), and butyrate or saline enemas administered. Mucosal barrier function was assessed by electrical resistance and 14C-mannitol permeability. HSP70 production was determined by 35S-methionine labelling, western blot and immunohistochemistry. Activation of heat shock factors(HSF) and nuclear factor kappa B (NF-{kappa}B) was evaluated by electrophoretic mobility shift assay (EMSA). Butyrate showed a significant protection against the decrease in cell viability, increase in mucosal permeability and polymorphonuclear neutrophil infiltration seen in DSS colitis. Butyrate inhibited HSP70 expression in DSS colitis and also inhibited the activation of HSF and of NF{kappa}B. Thus, butyrate enema was found to be cytoprotective in DSS colitis, an effect partly mediated by suppressing activation of HSP70 and NF-{kappa}B.




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