Interleukin-11-induced heat shock protein 25 confers intestinal epithelial-specific cytoprotection from oxidant stress.
BACKGROUND & AIMS: The mechanisms of interleukin-11 (IL-11) cytoprotection in intestinal epithelial injury are largely unknown. IL-11 protects barrier integrity during oxidant stress, a common endpoint of numerous types of intestinal injury including ischemia and immune-mediated inflammation. Because heat shock proteins (hsp) are cytoprotective in intestinal epithelia, we hypothesized that IL-11-conferred cytoprotection is mediated by inducible hsps. METHODS: IL-11 receptor (IL-11R) activation was determined using phospho-specific antibodies to STAT3. IL-11 induction of hsp72 and hsp25 was determined by immunoblot in IEC-18 crypt and young adult mouse colon colonic epithelial cells. Epithelial resistance to oxidant injury by monochloramine was determined by (51)Cr release. Stable hsp anti-sense IEC-18 cell clones were obtained by electroporation and hygromycin B selection. The IL-11 effect on hsp25 distribution was characterized by analysis of Triton x-100 insoluble fractions, 2-D isoelectric focusing gels, and confocal microscopy. RESULTS: IL-11R signaling was detected in all cells under study. IL-11 induces hsp25 in an intestinal epithelial-specific manner that significantly preserves cellular viability in the presence of monochloramine. This effect was significantly reversed in intestinal epithelia stably expressing anti-sense to hsp25. IL-11 induced a shift of hsp25 to Triton x-100 insoluble fractions containing cytoskeletal elements, which was not associated with altered hsp25 phosphorylation. The shift was not paralleled by increased hsp25 co-localization with F-actin by confocal microscopy. CONCLUSIONS: The induction of hsp25 by IL-11 confers epithelial-specific cytoprotection that is independent of phosphorylation-dependent co-localization of hsp25 to F-actin, thereby contributing to the protective effects of IL-11 in models of intestinal epithelial injury.[1]References
- Interleukin-11-induced heat shock protein 25 confers intestinal epithelial-specific cytoprotection from oxidant stress. Ropeleski, M.J., Tang, J., Walsh-Reitz, M.M., Musch, M.W., Chang, E.B. Gastroenterology (2003) [Pubmed]
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