Rho kinase signalling mediates radiation-induced inflammation and intestinal barrier dysfunction.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1711568
- author
- Röme, Andrada LU ; Santén, Stefan LU ; Jeppsson, Bengt LU and Thorlacius, Henrik LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British Journal of Surgery
- volume
- 98
- pages
- 124 - 131
- publisher
- Oxford University Press
- external identifiers
-
- wos:000285253700021
- pmid:20882561
- scopus:78650113104
- pmid:20882561
- 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
- 2016-04-04 08:10:16
- date last changed
- 2022-01-29 03:05:17
@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 < 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.}}, author = {{Röme, Andrada and Santén, Stefan and Jeppsson, Bengt and Thorlacius, Henrik}}, issn = {{1365-2168}}, language = {{eng}}, pages = {{124--131}}, publisher = {{Oxford University Press}}, 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}}, doi = {{10.1002/bjs.7279}}, volume = {{98}}, year = {{2011}}, }