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Rho kinase signalling mediates radiation-induced inflammation and intestinal barrier dysfunction.

Röme, Andrada LU ; Santén, Stefan LU ; Jeppsson, Bengt LU and Thorlacius, Henrik LU (2011) In British Journal of Surgery 98. p.124-131
Abstract
BACKGROUND:: Radiotherapy is important in the management of pelvic malignancies, but radiation-induced intestinal damage is a dose-limiting factor. Microvascular injury and epithelial barrier dysfunction are considered to be rate-limiting aspects in radiation-induced enteropathy. This study investigated the role of Rho kinase signalling in radiation-induced inflammation and intestinal barrier dysfunction. METHODS:: The specific Rho kinase inhibitor Y-27632 (1 and 10 mg/kg) was given to C57BL/6J mice before challenge with 20 Gy radiation. Leucocyte- and platelet-endothelium interactions in the colonic microcirculation were assessed by intravital microscopy. Levels of myeloperoxidase (MPO) and CXC chemokines (macrophage inflammatory protein... (More)
BACKGROUND:: Radiotherapy is important in the management of pelvic malignancies, but radiation-induced intestinal damage is a dose-limiting factor. Microvascular injury and epithelial barrier dysfunction are considered to be rate-limiting aspects in radiation-induced enteropathy. This study investigated the role of Rho kinase signalling in radiation-induced inflammation and intestinal barrier dysfunction. METHODS:: The specific Rho kinase inhibitor Y-27632 (1 and 10 mg/kg) was given to C57BL/6J mice before challenge with 20 Gy radiation. Leucocyte- and platelet-endothelium interactions in the colonic microcirculation were assessed by intravital microscopy. Levels of myeloperoxidase (MPO) and CXC chemokines (macrophage inflammatory protein 2 and cytokine-induced neutrophil chemoattractant), and intestinal leakage were quantified after 16 h. RESULTS:: Radiation increased leucocyte and platelet recruitment, MPO activity, CXC chemokine production and intestinal leakage. Y-27632 significantly reduced radiation-induced leucocyte rolling and abolished adhesion; it also decreased platelet rolling and adhesion by 55 and 74 per cent respectively (P < 0·050). Inhibition of Rho kinase signalling significantly decreased radiation-provoked formation of CXC chemokines, MPO activity by 52 per cent, and intestinal leakage by 67 per cent (P < 0·050). CONCLUSION:: Rho kinase activity constitutes an important signalling mechanism in radiation-induced inflammation and intestinal barrier dysfunction. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. (Less)
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type
Contribution to journal
publication status
published
subject
in
British Journal of Surgery
volume
98
pages
124 - 131
publisher
John Wiley & Sons
external identifiers
  • wos:000285253700021
  • pmid:20882561
  • scopus:78650113104
ISSN
1365-2168
DOI
10.1002/bjs.7279
language
English
LU publication?
yes
id
6e733bc8-46f9-4735-bce1-8cf23f60127f (old id 1711568)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20882561?dopt=Abstract
date added to LUP
2010-11-03 18:27:53
date last changed
2017-10-22 04:53:34
@article{6e733bc8-46f9-4735-bce1-8cf23f60127f,
  abstract     = {BACKGROUND:: Radiotherapy is important in the management of pelvic malignancies, but radiation-induced intestinal damage is a dose-limiting factor. Microvascular injury and epithelial barrier dysfunction are considered to be rate-limiting aspects in radiation-induced enteropathy. This study investigated the role of Rho kinase signalling in radiation-induced inflammation and intestinal barrier dysfunction. METHODS:: The specific Rho kinase inhibitor Y-27632 (1 and 10 mg/kg) was given to C57BL/6J mice before challenge with 20 Gy radiation. Leucocyte- and platelet-endothelium interactions in the colonic microcirculation were assessed by intravital microscopy. Levels of myeloperoxidase (MPO) and CXC chemokines (macrophage inflammatory protein 2 and cytokine-induced neutrophil chemoattractant), and intestinal leakage were quantified after 16 h. RESULTS:: Radiation increased leucocyte and platelet recruitment, MPO activity, CXC chemokine production and intestinal leakage. Y-27632 significantly reduced radiation-induced leucocyte rolling and abolished adhesion; it also decreased platelet rolling and adhesion by 55 and 74 per cent respectively (P &lt; 0·050). Inhibition of Rho kinase signalling significantly decreased radiation-provoked formation of CXC chemokines, MPO activity by 52 per cent, and intestinal leakage by 67 per cent (P &lt; 0·050). CONCLUSION:: Rho kinase activity constitutes an important signalling mechanism in radiation-induced inflammation and intestinal barrier dysfunction. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley &amp; Sons, Ltd.},
  author       = {Röme, Andrada and Santén, Stefan and Jeppsson, Bengt and Thorlacius, Henrik},
  issn         = {1365-2168},
  language     = {eng},
  pages        = {124--131},
  publisher    = {John Wiley & Sons},
  series       = {British Journal of Surgery},
  title        = {Rho kinase signalling mediates radiation-induced inflammation and intestinal barrier dysfunction.},
  url          = {http://dx.doi.org/10.1002/bjs.7279},
  volume       = {98},
  year         = {2011},
}