Intestinal Epithelium Expresses TLR4 In Response To Ischemia

Susan M. Suozzo and Sherry D. Fleming. Kansas State University, Manhattan, KS

Background and Objective: During intestinal surgery, the intestine experiences ischemia which induces immediate cellular damage that is significantly magnified by reperfusion. Intestinal ischemia/reperfusion (IR) damages epithelial cells, critical for maintaining a barrier against pathogens.  Recognizing conserved microbial motifs, Toll-like receptors (TLRs) may be candidate molecules in the mechanism of damage. The intestinal epithelium expresses TLR4 which engages lipopolysaccharide on Gram negative bacteria to induce the inflammatory response. During surgery, intestinal TLR4 expression is regulated to prevent pathological inflammation. The specific cells expressing TLR4 are unknown. The hypothesis is that TLR4 expression on intestinal epithelial cells is altered by IR.

Methods: Mice were subjected to 30 minutes intestinal ischemia followed by 2 hours reperfusion and intestinal samples collected. Laser capture microdissection isolated the intestinal epithelial cells and gene expression was analyzed by RT-PCR. Results: Epithelial cells (verified by RT-PCR) from mice subjected to IR expressed increased TLR4 mRNA compared to cells from sham treated mice.

Discussion and Conclusions: These data support our hypothesis that ischemia induces epithelial TLR4 mRNA expression and correlates with epithelial damage induced by IR. Therefore, TLR4 may be a therapeutic target for future studies.

Acknowledgements: NIH IDeA Grants P20 RR017686 and RR016475 and AI061691, American Heart Association, NSF SBE-0244984, KSU Cancer Center and Division of Biology. Any opinions, findings, and conclusions expressed are the authors and not the views of NSF or NIH.

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