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p38 MAPK regulates ischemia-reperfusion-induced recruitment of leukocytes in the colon.

Santén, Stefan LU ; Röme, Andrada LU ; Laschke, Matthias LU ; Menger, Michael D; Wang, Yousheng; Jeppsson, Bengt LU and Thorlacius, Henrik LU (2009) In Surgery 145(3). p.303-312
Abstract
BACKGROUND: Our objective was to examine the role of p38 mitogen-activated protein kinase (MAPK) in ischemia-reperfusion (I/R)-induced recruitment or leukocytes in the colon. METHODS: C57/Bl6 mice were subjected to 30 minutes of ischemia by clamping the superior mesenteric artery followed by 2 hours of reperfusion. Animals were pretreated with the selective p38 MAPK inhibitors SB 239063 and SKF 86002 before induction of I/R. Leukocyte-endothelium interactions were quantified by use of intravital fluorescence microscopy. Additionally, the role of p38 MAPK in mast cell-generated tumor necrosis factor-alpha (TNF-alpha) as well as neutrophil adhesion and P-selectin expression were examined in vitro. RESULTS: SB 239063 and SKF 86002 decreased... (More)
BACKGROUND: Our objective was to examine the role of p38 mitogen-activated protein kinase (MAPK) in ischemia-reperfusion (I/R)-induced recruitment or leukocytes in the colon. METHODS: C57/Bl6 mice were subjected to 30 minutes of ischemia by clamping the superior mesenteric artery followed by 2 hours of reperfusion. Animals were pretreated with the selective p38 MAPK inhibitors SB 239063 and SKF 86002 before induction of I/R. Leukocyte-endothelium interactions were quantified by use of intravital fluorescence microscopy. Additionally, the role of p38 MAPK in mast cell-generated tumor necrosis factor-alpha (TNF-alpha) as well as neutrophil adhesion and P-selectin expression were examined in vitro. RESULTS: SB 239063 and SKF 86002 decreased both I/R-provoked leukocyte rolling and adhesion by > 75%. Inhibition of p38 MAPK decreased dose-dependently the mast cell generated TNF-alpha production as well as TNF-alpha-induced expression of P-selectin and neutrophil adhesion on endothelial cells. CONCLUSION: We conclude that p38 MAPK regulates leukocyte rolling and adhesion in colonic I/R. Moreover, inhibition of p38 MAPK activity decreases formation of TNF-alpha and P-selectin-dependent leukocyte attachment to activated endothelial cells. Thus, our findings suggest that interference with the p38 MAPK signaling pathway could be an effective strategy to protect against I/R-induced inflammation in the colon. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Surgery
volume
145
issue
3
pages
303 - 312
publisher
Elsevier
external identifiers
  • WOS:000263736800008
  • PMID:19231583
  • Scopus:60149086844
ISSN
1532-7361
DOI
10.1016/j.surg.2008.10.011
language
English
LU publication?
yes
id
9700ea83-940f-4f24-a80b-5b834e9cc1f3 (old id 1302347)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19231583?dopt=Abstract
date added to LUP
2009-03-03 12:07:14
date last changed
2016-10-13 04:28:34
@misc{9700ea83-940f-4f24-a80b-5b834e9cc1f3,
  abstract     = {BACKGROUND: Our objective was to examine the role of p38 mitogen-activated protein kinase (MAPK) in ischemia-reperfusion (I/R)-induced recruitment or leukocytes in the colon. METHODS: C57/Bl6 mice were subjected to 30 minutes of ischemia by clamping the superior mesenteric artery followed by 2 hours of reperfusion. Animals were pretreated with the selective p38 MAPK inhibitors SB 239063 and SKF 86002 before induction of I/R. Leukocyte-endothelium interactions were quantified by use of intravital fluorescence microscopy. Additionally, the role of p38 MAPK in mast cell-generated tumor necrosis factor-alpha (TNF-alpha) as well as neutrophil adhesion and P-selectin expression were examined in vitro. RESULTS: SB 239063 and SKF 86002 decreased both I/R-provoked leukocyte rolling and adhesion by > 75%. Inhibition of p38 MAPK decreased dose-dependently the mast cell generated TNF-alpha production as well as TNF-alpha-induced expression of P-selectin and neutrophil adhesion on endothelial cells. CONCLUSION: We conclude that p38 MAPK regulates leukocyte rolling and adhesion in colonic I/R. Moreover, inhibition of p38 MAPK activity decreases formation of TNF-alpha and P-selectin-dependent leukocyte attachment to activated endothelial cells. Thus, our findings suggest that interference with the p38 MAPK signaling pathway could be an effective strategy to protect against I/R-induced inflammation in the colon.},
  author       = {Santén, Stefan and Röme, Andrada and Laschke, Matthias and Menger, Michael D and Wang, Yousheng and Jeppsson, Bengt and Thorlacius, Henrik},
  issn         = {1532-7361},
  language     = {eng},
  number       = {3},
  pages        = {303--312},
  publisher    = {ARRAY(0x91f5d60)},
  series       = {Surgery},
  title        = {p38 MAPK regulates ischemia-reperfusion-induced recruitment of leukocytes in the colon.},
  url          = {http://dx.doi.org/10.1016/j.surg.2008.10.011},
  volume       = {145},
  year         = {2009},
}