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MINERVA ANESTESIOLOGICA

A Journal on Anesthesiology, Resuscitation, Analgesia and Intensive Care


Official Journal of the Italian Society of Anesthesiology, Analgesia, Resuscitation and Intensive Care
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Minerva Anestesiologica 2017 Apr 13

DOI: 10.23736/S0375-9393.17.11715-3

Copyright © 2017 EDIZIONI MINERVA MEDICA

language: English

Colon epithelial injury in critically ill colectomized patients: aberration of tight junction proteins and Toll-like receptors

Seija SIPOLA 1, 2 , Tero I. ALA-KOKKO 1, 2, Jouko J. LAURILA 1, 2, Juha SAARNIO 2, 3, Pasi OHTONEN 2, 3, Hannu SYRJÄLÄ 2, 4, Tuomo J. KARTTUNEN 2, 5


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BACKGROUND: Abnormal permeability and extensive epithelial injury are characteristic of colon wall damage complicating critical illness, such as sepsis, and associated with mortality. To assess mechanisms of such colon epithelial disruption, we studied expression of markers of innate immunity and intercellular junctions in patients with critical illness.
METHODS: Emergency colectomy samples from 38 intensive care unit patients with sepsis, fulminant C. difficile colitis, or colon ischemia were studied. Expression of tight junction proteins (claudin-1, claudin-2, occludin) and Toll-like receptors (TLRs) (TLR2, TLR4, TLR5, and TLR9) was studied in samples representing histologically verified damaged segments of the colon, and compared with normal colon (n=28).
RESULTS: As compared with normal epithelium, histologically damaged samples showed decreased claudin-1 (p=0.002) expression. Expression of TLR2, TLR4, and TLR5 was similar in patients and controls, but TLR9 expression was up-regulated in the histologically damaged region (p=0.03). The expression of other markers (claudin-1, claudin-2, occludin, TLR2,TLR4, TLR5 and TLR9) did not differ between survivors and non-survivors.
CONCLUSIONS: Down-regulation of claudin-1 and up-regulation of TLR9 suggest that epithelial barrier dysfunction and innate immunity activation are involved in the pathogenesis of colon epithelial injury in patients with critical illness.


KEY WORDS: Critically ill - Toll-like receptor - Tight junction - Colon injury - Epithelial barrier dysfunction

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1 Department of Anesthesiology, Division of Intensive Care Medicine, University Hospital of Oulu, Oulu, Finland; 2 Medical Research Center, Research Group of Surgery, Anesthesia and Intensive Care, Medical Faculty, University of Oulu, Oulu, Finland; 3 Department of Surgery, University Hospital of Oulu, Oulu, Finland; 4 Department of Infection Control and Institute of Diagnostics, University Hospital of Oulu, Oulu, Finland; 5 Oulu University Hospital, Department of Pathology, University Hospital of Oulu, Oulu, Finland