Short-chain fatty acids induce intestinal epithelial heat shock protein 25expression in rats and IEC 18 cells

Background & Aims: Because short-chain fatty acids (SCFAs) and heat shock p roteins (hsps) confer protection to intestinal epithelia cells (IECs), we s tudied whether SCFAs modulate IEC hsp expression. Methods: Hsp 25, hsp72, a nd hsc73 protein expression in rat intestinal tissues and IEC-18 cells were determined by Western blot and immunohistochemistry. Cell survival under c onditions of oxidant stress (monochloramine) was determined using Cr-51 rel ease in hsp25 cDNA antisense and sense-transfected cells expressing minimal and increased hsp25, respectively. Results: Butyrate induces a time- and c oncentration-dependent increase in hsp25, but not hsp72 or hsc73, protein e xpression in rat IEC-18 cells but not 3T3 fibroblasts. Other SCFAs, includi ng the poorly metabolized isobutyate, also induced selective expression of hsp25. Butyrate treatment significantly improved the ability of IEC-18 cell s to withstand oxidant (monochloramine) injury. This effect could be blocke d in cells in which hsp25 induction by butyrate was blocked by stable hsp25 antisense transfection. Additionally, hsp25-transfected overexpressing IEC -18 cells showed increased resistance to monochloramine. In vivo, increasin g dietary fiber increased colonic, but not proximal, ileal hsp25 while havi ng no effect on hsp72 or hsc73 expression. Conclusions: SCFAs, the predomin ant anions of colonic fluid derived from bacterial flora metabolism of lumi nal carbohydrates, protect IECs against oxidant injury, an effect mediated in part by cell-specific hsp25 induction.