Rho-kinase signalling regulates CXC chemokine formation and leukocyte recruitment in colonic ischemia-reperfusion
- PMID: 20593289
- DOI: 10.1007/s00384-010-0997-3
Rho-kinase signalling regulates CXC chemokine formation and leukocyte recruitment in colonic ischemia-reperfusion
Abstract
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.
Similar articles
-
Mast-cell-dependent secretion of CXC chemokines regulates ischemia-reperfusion-induced leukocyte recruitment in the colon.Int J Colorectal Dis. 2008 May;23(5):527-34. doi: 10.1007/s00384-007-0436-2. Epub 2008 Jan 11. Int J Colorectal Dis. 2008. PMID: 18193431
-
Oxygen radical-dependent expression of CXC chemokines regulate ischemia/reperfusion-induced leukocyte adhesion in the mouse colon.Free Radic Biol Med. 2003 Oct 1;35(7):782-9. doi: 10.1016/s0891-5849(03)00405-2. Free Radic Biol Med. 2003. PMID: 14583342
-
P-selectin glycoprotein ligand-1 regulates chemokine-dependent leukocyte recruitment in colonic ischemia-reperfusion.Inflamm Res. 2007 Nov;56(11):452-8. doi: 10.1007/s00011-007-7071-9. Inflamm Res. 2007. PMID: 17891336
-
p38 MAPK regulates ischemia-reperfusion-induced recruitment of leukocytes in the colon.Surgery. 2009 Mar;145(3):303-12. doi: 10.1016/j.surg.2008.10.011. Epub 2009 Feb 1. Surgery. 2009. PMID: 19231583
-
The Importance of CXCL1 in the Physiological State and in Noncancer Diseases of the Oral Cavity and Abdominal Organs.Int J Mol Sci. 2022 Jun 28;23(13):7151. doi: 10.3390/ijms23137151. Int J Mol Sci. 2022. PMID: 35806156 Free PMC article. Review.
Cited by
-
The effect of Rho kinase inhibitor Y-27632 on endotoxemia-induced intestinal apoptosis in infant rats.J Mol Histol. 2012 Feb;43(1):81-7. doi: 10.1007/s10735-011-9379-6. Epub 2011 Dec 6. J Mol Histol. 2012. PMID: 22143494
-
Hydrogen sulfide improves intestinal recovery following ischemia by endothelial nitric oxide-dependent mechanisms.Am J Physiol Gastrointest Liver Physiol. 2017 May 1;312(5):G450-G456. doi: 10.1152/ajpgi.00444.2016. Epub 2017 Mar 9. Am J Physiol Gastrointest Liver Physiol. 2017. PMID: 28280145 Free PMC article.
-
Epithelial cell-specific MyD88 signaling mediates ischemia/reperfusion-induced intestinal injury independent of microbial status.Inflamm Bowel Dis. 2013 Dec;19(13):2857-66. doi: 10.1097/01.MIB.0000435445.96933.37. Inflamm Bowel Dis. 2013. PMID: 24141713 Free PMC article.
-
Rho kinase regulates induction of T-cell immune dysfunction in abdominal sepsis.Infect Immun. 2013 Jul;81(7):2499-506. doi: 10.1128/IAI.00126-13. Epub 2013 Apr 29. Infect Immun. 2013. PMID: 23630965 Free PMC article.
-
Rho-kinase signalling regulates trypsinogen activation and tissue damage in severe acute pancreatitis.Br J Pharmacol. 2011 Feb;162(3):648-58. doi: 10.1111/j.1476-5381.2010.01060.x. Br J Pharmacol. 2011. PMID: 20942858 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous