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- Santén, StefanLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups (författare)
Rho-kinase signalling regulates CXC chemokine formation and leukocyte recruitment in colonic ischemia-reperfusion.
- Artikel/kapitelEngelska2010
Förlag, utgivningsår, omfång ...
- 2010-07-01
- Springer Science and Business Media LLC,2010
Nummerbeteckningar
- LIBRIS-ID:oai:lup.lub.lu.se:b4c0aa56-f35c-4634-945d-7ffe3e7e4d75
- https://lup.lub.lu.se/record/1645380URI
- https://doi.org/10.1007/s00384-010-0997-3DOI
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- Språk:engelska
- Sammanfattning på:engelska
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- BACKGROUND AND AIMS: Leukocyte recruitment is a key feature in ischemia-reperfusion (I/R)-induced tissue injury. The aim of the present study was to investigate the effect of Rho-kinase inhibition on I/R-provoked leukocyte recruitment in the colon. METHODS: C57BL/6 mice were subjected to 30 min of ischemia by clamping of the superior mesenteric artery followed by 120 min of reperfusion. Intraperitoneal pretreatment with the selective Rho-kinase inhibitors fasudil (4-40 mg/kg) and Y-27632 (1-10 mg/kg) was administered prior to induction of colonic I/R. Leukocyte-endothelium interactions were analyzed by intravital fluorescence microscopy. Colonic content of tumour necrosis factor-alpha (TNF-alpha) and the CXC chemokines macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC) were determined by ELISA. Additionally, colonic activity of myeloperoxidase (MPO), a marker of leukocyte infiltration, and malondialdehyde (MDA), were quantified. RESULTS: Fasudil and Y-27632 pretreatment decreased I/R-induced leukocyte rolling and adhesion by 76% and 96%, respectively. Moreover, Rho-kinase interference reduced formation of TNF-alpha, MIP-2 and KC by more than 68% in the reperfused colon. Additionally, the reperfusion-provoked increase in the levels of MPO and MDA in the colon decreased after Rho-kinase inhibition by 69% and 42%, respectively. CONCLUSIONS: Our data demonstrate that inhibition of Rho-kinase activity decrease I/R-induced leukocyte rolling, adhesion and recruitment in the colon. Moreover, these findings show that Rho-kinase signalling regulates TNF-alpha and CXC chemokine formation as well as lipid peroxidation in the reperfused colon. Thus, targeting Rho-kinase signalling may be a useful strategy in order to protect against pathological inflammation in the colon.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
- Wang, YushengLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups(Swepub:lu)yu4833wa (författare)
- Laschke, MatthiasLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups(Swepub:lu)med-mls (författare)
- Menger, Michael D (författare)
- Jeppsson, BengtLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups(Swepub:lu)kir-bje (författare)
- Thorlacius, HenrikLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups(Swepub:lu)kir-hth (författare)
- KirurgiForskargrupper vid Lunds universitet (creator_code:org_t)
Sammanhörande titlar
- Ingår i:International Journal of Colorectal Disease: Springer Science and Business Media LLC25, s. 1063-10701432-12620179-1958
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- International Journal of Colorectal Disease (Sök värdpublikationen i LIBRIS)
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