Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-2-9
pubmed:abstractText
CXC chemokines, including human interleukin-8 and rat cytokine-induced neutrophil chemoattractant-1, play a crucial role in the pathogenesis of intestinal inflammation induced by ischemia-reperfusion (I-R). Thrombin and its specific receptor, protease-activated receptor 1 (PAR1), act as important players in inflammation. However, the association between thrombin activation and chemokine production during I-R has not been well studied. We investigated whether thrombin and PAR1 might be involved in the pathophysiology of intestinal I-R, using an in vivo model. Intestinal damage was induced by clamping the superior mesenteric artery for 30 min followed by reperfusion in male Wistar rats. Thrombin-antithrombin complex was measured as an indicator of thrombin activation. PAR1 expression in the intestine was evaluated by real-time PCR. The severity of the intestinal mucosal injury was evaluated on the distal segment of the ileum by several biochemical markers and histological findings. Reperfusion significantly increased the serum levels of thrombin-antithrombin complex and enhanced PAR1 expression in the intestinal mucosa. The levels of both intraluminal hemoglobin and protein were significantly increased in the I-R group. The mucosal myeloperoxidase activity and expressions and/or productions of cytokine-induced neutrophil chemoattractant-1 and TNF-alpha were significantly increased after I-R. These increases were inhibited by the treatment of rat with antithrombin intravenously before I-R at a dose of 30 U/kg. These results suggest that the thrombin/PAR1 pathway plays an important role in the production of these cytokines during I-R and that antithrombin exerts potent anti-inflammatory effects on this injury via inhibition of proinflammatory cytokines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antithrombin III, http://linkedlifedata.com/resource/pubmed/chemical/Antithrombins, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL1, http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC, http://linkedlifedata.com/resource/pubmed/chemical/Cxcl1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Hemoglobins, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Peroxidase, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, PAR-1, http://linkedlifedata.com/resource/pubmed/chemical/Thrombin, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/antithrombin III-protease complex
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
292
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G678-83
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17023547-Animals, pubmed-meshheading:17023547-Antithrombin III, pubmed-meshheading:17023547-Antithrombins, pubmed-meshheading:17023547-Chemokine CXCL1, pubmed-meshheading:17023547-Chemokines, CXC, pubmed-meshheading:17023547-Gene Expression, pubmed-meshheading:17023547-Hemoglobins, pubmed-meshheading:17023547-Ileum, pubmed-meshheading:17023547-Intestinal Mucosa, pubmed-meshheading:17023547-Intestine, Small, pubmed-meshheading:17023547-Intestines, pubmed-meshheading:17023547-Male, pubmed-meshheading:17023547-Peptide Hydrolases, pubmed-meshheading:17023547-Peroxidase, pubmed-meshheading:17023547-RNA, Messenger, pubmed-meshheading:17023547-Rats, pubmed-meshheading:17023547-Rats, Wistar, pubmed-meshheading:17023547-Receptor, PAR-1, pubmed-meshheading:17023547-Reperfusion Injury, pubmed-meshheading:17023547-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17023547-Signal Transduction, pubmed-meshheading:17023547-Thrombin, pubmed-meshheading:17023547-Tumor Necrosis Factor-alpha
pubmed:year
2007
pubmed:articleTitle
Role of the thrombin/protease-activated receptor 1 pathway in intestinal ischemia-reperfusion injury in rats.
pubmed:affiliation
Department of Inflammation and Immunology, Kyoto Prefectural Univ of Medicine, Kawaramachi-Hirokoji, Kyoto, Japan.
pubmed:publicationType
Journal Article