p38 MAPK regulates ischemia-reperfusion-induced recruitment of leukocytes in the colon.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1302347
- author
- Santén, Stefan LU ; Röme, Andrada LU ; Laschke, Matthias LU ; Menger, Michael D ; Wang, Yousheng ; Jeppsson, Bengt LU and Thorlacius, Henrik LU
- organization
- publishing date
- 2009
- 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
- pmid:19231583
- ISSN
- 1532-7361
- DOI
- 10.1016/j.surg.2008.10.011
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200), Surgery Research Unit (013242220)
- 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
- 2016-04-04 09:19:57
- date last changed
- 2022-03-08 00:09:58
@article{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 = {{Elsevier}},
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}},
doi = {{10.1016/j.surg.2008.10.011}},
volume = {{145}},
year = {{2009}},
}