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: 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.
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Authors | A Mihaescu, S Santén, B Jeppsson, H Thorlacius |
Journal | The British journal of surgery
(Br J Surg)
Vol. 98
Issue 1
Pg. 124-31
(Jan 2011)
ISSN: 1365-2168 [Electronic] England |
PMID | 20882561
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. |
Chemical References |
- Amides
- Biomarkers
- Chemokines
- Enzyme Inhibitors
- Pyridines
- Y 27632
- Peroxidase
- rho-Associated Kinases
|
Topics |
- Amides
(pharmacology)
- Animals
- Biomarkers
- Chemokines
(metabolism)
- Colitis
(enzymology)
- Colon
(radiation effects)
- Enzyme Inhibitors
(pharmacology)
- Enzyme-Linked Immunosorbent Assay
- Leukocytes
(enzymology)
- Male
- Mice
- Mice, Inbred C57BL
- Permeability
- Peroxidase
(metabolism)
- Platelet Activation
(physiology)
- Pyridines
(pharmacology)
- Radiation Injuries, Experimental
(enzymology)
- Signal Transduction
(physiology)
- rho-Associated Kinases
(antagonists & inhibitors, physiology)
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