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Active site-inactivated factor VIIa inhibits nuclear factor kappa B activation in intestinal ischemia and reperfusion.

Stollenwerk, Maria; Lasson, Åke and Andersson, Roland LU (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:
author
organization
publishing date
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
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
2012-09-05 20:56:13
date last changed
2016-10-13 04:30:03
@misc{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    = {ARRAY(0xa231548)},
  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},
  volume       = {178},
  year         = {2012},
}