Active site-inactivated factor VIIa inhibits nuclear factor kappa B activation in intestinal ischemia and reperfusion.
(2012) In The Journal of surgical research 178(2). p.692-699- Abstract
- BACKGROUND:
Intestinal ischemia and reperfusion (I/R) injury is a pivotal mechanism in critical illness and in the development of multiple organ dysfunction syndrome, in which the nuclear factor kappa B (NF-κB) activation plays a central role. Intestinal I/R injury initiates the extrinsic tissue factor or factor VIIa-dependent pathway of coagulation, also of importance in multiple organ dysfunction syndrome. Our aim was to analyze NF-κB activation in I/R injury in the rat intestine and in two main "shock" organs, that is, the liver and lungs. Pretreatment with active site-inactivated factor VII (FVIIai), an inhibitor of the extrinsic pathway, was evaluated.
MATERIALS AND METHODS:
NF-κB activation was... (More) - BACKGROUND:
Intestinal ischemia and reperfusion (I/R) injury is a pivotal mechanism in critical illness and in the development of multiple organ dysfunction syndrome, in which the nuclear factor kappa B (NF-κB) activation plays a central role. Intestinal I/R injury initiates the extrinsic tissue factor or factor VIIa-dependent pathway of coagulation, also of importance in multiple organ dysfunction syndrome. Our aim was to analyze NF-κB activation in I/R injury in the rat intestine and in two main "shock" organs, that is, the liver and lungs. Pretreatment with active site-inactivated factor VII (FVIIai), an inhibitor of the extrinsic pathway, was evaluated.
MATERIALS AND METHODS:
NF-κB activation was analyzed using enzyme-linked immunosorbent assay (ELISA) and electrophoretic mobility shift assay (EMSA) studies of nuclear extracts from the intestine, liver, and lungs in rats subjected to intestinal I/R injury. FVIIai was given 90min before the induction of intestinal ischemia.
RESULTS:
I/R induced NF-κB p65 activation in all three organs, especially in the liver. Pretreatment with FVIIai counteracted NF-κB activation in all three tissues studied. A commercially available ELISA for (human) NF-κB p65 and EMSA gave parallel results.
CONCLUSIONS:
I/R injury in the rat intestine induces a pronounced activation of NF-κB p50 or p65 in the small intestine and in the liver and lungs. The NF-κB activation is especially pronounced in the liver and plays a central role in the regulation of transcription of cytokines, adhesion molecules, and chemokines. ELISA for (human) NF-κB p65 and "gold standard" EMSA gave parallel results. Pretreatment with FVIIai completely counteracted NF-κB activation in the intestine and liver, although not in the lungs. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3047233
- author
- Stollenwerk, Maria ; Lasson, Åke and Andersson, Roland LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Journal of surgical research
- volume
- 178
- issue
- 2
- pages
- 692 - 699
- publisher
- Elsevier
- external identifiers
-
- wos:000311090700031
- pmid:22920553
- scopus:84869082782
- pmid:22920553
- ISSN
- 1095-8673
- DOI
- 10.1016/j.jss.2012.07.056
- language
- English
- LU publication?
- yes
- id
- 9f2a2353-9c6c-4903-b2c4-fb5955e841fc (old id 3047233)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22920553?dopt=Abstract
- date added to LUP
- 2016-04-04 09:24:50
- date last changed
- 2022-01-29 17:43:57
@article{9f2a2353-9c6c-4903-b2c4-fb5955e841fc,
abstract = {{BACKGROUND: <br/><br>
Intestinal ischemia and reperfusion (I/R) injury is a pivotal mechanism in critical illness and in the development of multiple organ dysfunction syndrome, in which the nuclear factor kappa B (NF-κB) activation plays a central role. Intestinal I/R injury initiates the extrinsic tissue factor or factor VIIa-dependent pathway of coagulation, also of importance in multiple organ dysfunction syndrome. Our aim was to analyze NF-κB activation in I/R injury in the rat intestine and in two main "shock" organs, that is, the liver and lungs. Pretreatment with active site-inactivated factor VII (FVIIai), an inhibitor of the extrinsic pathway, was evaluated. <br/><br>
<br/><br>
MATERIALS AND METHODS: <br/><br>
NF-κB activation was analyzed using enzyme-linked immunosorbent assay (ELISA) and electrophoretic mobility shift assay (EMSA) studies of nuclear extracts from the intestine, liver, and lungs in rats subjected to intestinal I/R injury. FVIIai was given 90min before the induction of intestinal ischemia. <br/><br>
<br/><br>
RESULTS: <br/><br>
I/R induced NF-κB p65 activation in all three organs, especially in the liver. Pretreatment with FVIIai counteracted NF-κB activation in all three tissues studied. A commercially available ELISA for (human) NF-κB p65 and EMSA gave parallel results. <br/><br>
<br/><br>
CONCLUSIONS:<br/><br>
I/R injury in the rat intestine induces a pronounced activation of NF-κB p50 or p65 in the small intestine and in the liver and lungs. The NF-κB activation is especially pronounced in the liver and plays a central role in the regulation of transcription of cytokines, adhesion molecules, and chemokines. ELISA for (human) NF-κB p65 and "gold standard" EMSA gave parallel results. Pretreatment with FVIIai completely counteracted NF-κB activation in the intestine and liver, although not in the lungs.}},
author = {{Stollenwerk, Maria and Lasson, Åke and Andersson, Roland}},
issn = {{1095-8673}},
language = {{eng}},
number = {{2}},
pages = {{692--699}},
publisher = {{Elsevier}},
series = {{The Journal of surgical research}},
title = {{Active site-inactivated factor VIIa inhibits nuclear factor kappa B activation in intestinal ischemia and reperfusion.}},
url = {{http://dx.doi.org/10.1016/j.jss.2012.07.056}},
doi = {{10.1016/j.jss.2012.07.056}},
volume = {{178}},
year = {{2012}},
}