Short-chain fatty acids induce intestinal epithelial heat shock protein 25 expression in rats and IEC 18 cells.
OBJECTIVE
Because short-chain fatty acids (SCFAs) and heat shock proteins (hsps) confer protection to intestinal epithelia cells (IECs), we studied whether SCFAs modulate IEC hsp expression.


METHODS
Hsp 25, hsp72, and hsc73 protein expression in rat intestinal tissues and IEC-18 cells were determined by Western blot and immunohistochemistry. Cell survival under conditions of oxidant stress (monochloramine) was determined using (51)Cr release in hsp25 cDNA anti-sense and sense-transfected cells expressing minimal and increased hsp25, respectively.


RESULTS
Butyrate induces a time- and concentration-dependent increase in hsp25, but not hsp72 or hsc73, protein expression in rat IEC-18 cells but not 3T3 fibroblasts. Other SCFAs, including the poorly metabolized isobutyate, also induced selective expression of hsp25. Butyrate treatment significantly improved the ability of IEC-18 cells to withstand oxidant (monochloramine) injury. This effect could be blocked 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, increasing dietary fiber increased colonic, but not proximal, ileal hsp25 while having no effect on hsp72 or hsc73 expression.


CONCLUSIONS
SCFAs, the predominant anions of colonic fluid derived from bacterial flora metabolism of luminal carbohydrates, protect IECs against oxidant injury, an effect mediated in part by cell-specific hsp25 induction.
Ren
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The Martin Boyer Research Laboratories, The University of Chicago, Chicago, Illinois 60637, USA.
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Kojima
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Boone
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Chang
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D016475:3T3 Cells; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002700:Chloramines / Q000494:pharmacology; D003106:Colon / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D016373:DNA, Antisense; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007082:Ileum / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D018384:Oxidative Stress / Q000187:drug effects; D010368:Pectins / Q000494:pharmacology; D051381:Rats; D014162:Transfection
D000930:Antidiarrheals; D002087:Butyrates; D002700:Chloramines; D016373:DNA, Antisense; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; C486114:Hspb1 protein, rat; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D010368:Pectins; C030816:chloramine