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p38 Mitogen-activated protein kinase signalling regulates vascular inflammation and epithelial barrier dysfunction in an experimental model of radiation-induced colitis.

Röme, Andrada LU ; Santén, Stefan LU ; Jeppsson, Bengt LU and Thorlacius, Henrik LU (2010) In British Journal of Surgery 97. p.226-234
Abstract
BACKGROUND:: Microvascular injury and epithelial barrier dysfunction are rate-limiting aspects in radiation enteropathy. This study examined the role of p38 mitogen-activated protein kinase (p38 MAPK) signalling in radiation-induced colitis in an experimental model. METHODS:: The p38 MAPK inhibitor SB239063 was administered to mice immediately before exposure to 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 (MIP) 2 and cytokine-induced neutrophil chemoattractant (KC)), and albumin leakage were quantified 16 h after irradiation. RESULTS:: Irradiation induced an... (More)
BACKGROUND:: Microvascular injury and epithelial barrier dysfunction are rate-limiting aspects in radiation enteropathy. This study examined the role of p38 mitogen-activated protein kinase (p38 MAPK) signalling in radiation-induced colitis in an experimental model. METHODS:: The p38 MAPK inhibitor SB239063 was administered to mice immediately before exposure to 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 (MIP) 2 and cytokine-induced neutrophil chemoattractant (KC)), and albumin leakage were quantified 16 h after irradiation. RESULTS:: Irradiation induced an increase in leucocyte and platelet recruitment, MPO activity, CXC chemokine levels and intestinal leakage. Inhibition of p38 MAPK by SB239063 decreased radiation-induced leucocyte and platelet recruitment (leucocyte rolling and adhesion by 70 and 90 per cent, both P < 0.001; that of platelets by 70 and 74 per cent, both P < 0.001). It also reduced radiation-provoked increases in colonic MPO activity by 88 per cent (P < 0.001), formation of MIP-2 and KC by 72 and 74 per cent respectively (P = 0.003 and P < 0.001), and intestinal leakage by 81 per cent (P < 0.001). CONCLUSION:: p38 MAPK is an important signalling pathway in radiation-induced colitis. Copyright (c) 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. (Less)
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type
Contribution to journal
publication status
published
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in
British Journal of Surgery
volume
97
pages
226 - 234
publisher
John Wiley & Sons
external identifiers
  • wos:000274098100014
  • pmid:20034051
  • scopus:74549186985
ISSN
1365-2168
DOI
10.1002/bjs.6811
language
English
LU publication?
yes
id
53bf8c86-5e58-4975-a51c-625dde451c63 (old id 1523319)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20034051?dopt=Abstract
date added to LUP
2010-01-11 14:48:37
date last changed
2018-05-29 11:03:04
@article{53bf8c86-5e58-4975-a51c-625dde451c63,
  abstract     = {BACKGROUND:: Microvascular injury and epithelial barrier dysfunction are rate-limiting aspects in radiation enteropathy. This study examined the role of p38 mitogen-activated protein kinase (p38 MAPK) signalling in radiation-induced colitis in an experimental model. METHODS:: The p38 MAPK inhibitor SB239063 was administered to mice immediately before exposure to 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 (MIP) 2 and cytokine-induced neutrophil chemoattractant (KC)), and albumin leakage were quantified 16 h after irradiation. RESULTS:: Irradiation induced an increase in leucocyte and platelet recruitment, MPO activity, CXC chemokine levels and intestinal leakage. Inhibition of p38 MAPK by SB239063 decreased radiation-induced leucocyte and platelet recruitment (leucocyte rolling and adhesion by 70 and 90 per cent, both P &lt; 0.001; that of platelets by 70 and 74 per cent, both P &lt; 0.001). It also reduced radiation-provoked increases in colonic MPO activity by 88 per cent (P &lt; 0.001), formation of MIP-2 and KC by 72 and 74 per cent respectively (P = 0.003 and P &lt; 0.001), and intestinal leakage by 81 per cent (P &lt; 0.001). CONCLUSION:: p38 MAPK is an important signalling pathway in radiation-induced colitis. Copyright (c) 2009 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        = {226--234},
  publisher    = {John Wiley & Sons},
  series       = {British Journal of Surgery},
  title        = {p38 Mitogen-activated protein kinase signalling regulates vascular inflammation and epithelial barrier dysfunction in an experimental model of radiation-induced colitis.},
  url          = {http://dx.doi.org/10.1002/bjs.6811},
  volume       = {97},
  year         = {2010},
}