p38 Mitogen-activated protein kinase signalling regulates vascular inflammation and epithelial barrier dysfunction in an experimental model of radiation-induced colitis
| Autor: | Stefan Santen, Bengt Jeppsson, Andrada Mihaescu, Henrik Thorlacius |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Blood Platelets
Vasculitis medicine.medical_specialty Radiation Colitis Colon medicine.medical_treatment Inflammation Radiation enteropathy p38 Mitogen-Activated Protein Kinases Epithelium Leukocyte Count Mice Internal medicine medicine Leukocytes Animals Colitis Radiation Injuries Macrophage inflammatory protein biology business.industry medicine.disease Mice Inbred C57BL Endocrinology Cytokine Myeloperoxidase Immunology biology.protein Mice Inbred CBA Surgery medicine.symptom Chemokines business Intravital microscopy Signal Transduction |
| Zdroj: | The British journal of surgery. 97(2) |
| ISSN: | 1365-2168 |
| Popis: | BackgroundMicrovascular injury and epithelial barrier dysfunction are rate-limiting aspects in radiation enteropathy. This study examined the role of p38 mitogen-activated protein kinase (p38 MAPK) signalling in radiation-induced colitis in an experimental model.MethodsThe p38 MAPK inhibitor SB239063 was administered to mice immediately before exposure to 20 Gy radiation. Leucocyte– and platelet–endothelium interactions in the colonic microcirculation were assessed by intravital microscopy. Levels of myeloperoxidase (MPO) and CXC chemokines (macrophage inflammatory protein (MIP) 2 and cytokine-induced neutrophil chemoattractant (KC)), and albumin leakage were quantified 16 h after irradiation.ResultsIrradiation induced an increase in leucocyte and platelet recruitment, MPO activity, CXC chemokine levels and intestinal leakage. Inhibition of p38 MAPK by SB239063 decreased radiation-induced leucocyte and platelet recruitment (leucocyte rolling and adhesion by 70 and 90 per cent, both P < 0·001; that of platelets by 70 and 74 per cent, both P < 0·001). It also reduced radiation-provoked increases in colonic MPO activity by 88 per cent (P < 0·001), formation of MIP-2 and KC by 72 and 74 per cent respectively (P = 0·003 and P < 0·001), and intestinal leakage by 81 per cent (P < 0·001).Conclusionp38 MAPK is an important signalling pathway in radiation-induced colitis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text