Rho-kinase signalling mediates endotoxin hypersensitivity after partial hepatectomy.
(2008) In British Journal of Surgery Jun 18. p.976-984- Abstract
- BACKGROUND:: Excessive loss of functional liver mass results in hepatic dysfunction and is associated with an increased sensitivity to infection. This experimental study investigated the role of Rho-kinase in hepatectomy-induced sensitization to endotoxin. METHODS:: Male C57BL/6J mice underwent 68 per cent hepatectomy and were injected 24 h later with 100 microg Escherichia coli lipopolysaccharide (LPS). Simultaneously, animals received either fasudil or Y-27632 for Rho-kinase inhibition, or phosphate-buffered saline. Untreated hepatectomized animals served as positive controls and sham-operated animals as negative controls. Liver injury and inflammatory parameters were assessed 6 h after LPS challenge by serum alanine aminotransferase... (More)
- BACKGROUND:: Excessive loss of functional liver mass results in hepatic dysfunction and is associated with an increased sensitivity to infection. This experimental study investigated the role of Rho-kinase in hepatectomy-induced sensitization to endotoxin. METHODS:: Male C57BL/6J mice underwent 68 per cent hepatectomy and were injected 24 h later with 100 microg Escherichia coli lipopolysaccharide (LPS). Simultaneously, animals received either fasudil or Y-27632 for Rho-kinase inhibition, or phosphate-buffered saline. Untreated hepatectomized animals served as positive controls and sham-operated animals as negative controls. Liver injury and inflammatory parameters were assessed 6 h after LPS challenge by serum alanine aminotransferase (ALT) levels, histomorphology and enzyme-linked immunosorbent assay. RESULTS:: Hepatectomy resulted in a significant susceptibility to LPS, as indicated by inflammatory leucocyte recruitment (mean(s.e.m.) 10(1) leucocytes per high-power field), hepatocellular disintegration (ALT 22.4(3.1) microkat/l) and apoptotic cell death (3.8(0.2) per cent). Rho-kinase inhibition reduced leucocytic infiltration by more than 33 per cent, abolished hepatocellular apoptosis entirely, and reduced tumour necrosis factor alpha expression by more than 48 per cent and CXC chemokine expression by more than 36 per cent. CONCLUSION:: Hepatectomy increased susceptibility to LPS by Rho-kinase-dependent mechanisms. Blocking Rho-kinase signalling decreased LPS-induced liver injury in hepatectomized mice. Copyright (c) 2008 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/1168688
- author
- Slotta, J E ; Laschke, M W ; Menger, M D and Thorlacius, Henrik LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British Journal of Surgery
- volume
- Jun 18
- pages
- 976 - 984
- publisher
- Oxford University Press
- external identifiers
-
- wos:000258016200008
- pmid:18563790
- scopus:48249153495
- pmid:18563790
- ISSN
- 1365-2168
- DOI
- 10.1002/bjs.6082
- language
- English
- LU publication?
- yes
- id
- 300b24a5-f8b6-4120-aa1c-3b3603e1229d (old id 1168688)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18563790?dopt=Abstract
- date added to LUP
- 2016-04-04 08:48:35
- date last changed
- 2022-01-29 03:59:10
@article{300b24a5-f8b6-4120-aa1c-3b3603e1229d,
abstract = {{BACKGROUND:: Excessive loss of functional liver mass results in hepatic dysfunction and is associated with an increased sensitivity to infection. This experimental study investigated the role of Rho-kinase in hepatectomy-induced sensitization to endotoxin. METHODS:: Male C57BL/6J mice underwent 68 per cent hepatectomy and were injected 24 h later with 100 microg Escherichia coli lipopolysaccharide (LPS). Simultaneously, animals received either fasudil or Y-27632 for Rho-kinase inhibition, or phosphate-buffered saline. Untreated hepatectomized animals served as positive controls and sham-operated animals as negative controls. Liver injury and inflammatory parameters were assessed 6 h after LPS challenge by serum alanine aminotransferase (ALT) levels, histomorphology and enzyme-linked immunosorbent assay. RESULTS:: Hepatectomy resulted in a significant susceptibility to LPS, as indicated by inflammatory leucocyte recruitment (mean(s.e.m.) 10(1) leucocytes per high-power field), hepatocellular disintegration (ALT 22.4(3.1) microkat/l) and apoptotic cell death (3.8(0.2) per cent). Rho-kinase inhibition reduced leucocytic infiltration by more than 33 per cent, abolished hepatocellular apoptosis entirely, and reduced tumour necrosis factor alpha expression by more than 48 per cent and CXC chemokine expression by more than 36 per cent. CONCLUSION:: Hepatectomy increased susceptibility to LPS by Rho-kinase-dependent mechanisms. Blocking Rho-kinase signalling decreased LPS-induced liver injury in hepatectomized mice. Copyright (c) 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.}},
author = {{Slotta, J E and Laschke, M W and Menger, M D and Thorlacius, Henrik}},
issn = {{1365-2168}},
language = {{eng}},
pages = {{976--984}},
publisher = {{Oxford University Press}},
series = {{British Journal of Surgery}},
title = {{Rho-kinase signalling mediates endotoxin hypersensitivity after partial hepatectomy.}},
url = {{http://dx.doi.org/10.1002/bjs.6082}},
doi = {{10.1002/bjs.6082}},
volume = {{Jun 18}},
year = {{2008}},
}