Local and remote tissue injury upon intestinal ischemia and reperfusion depends on the TLR/MyD88 signaling pathway
Autor: | Bernardo Boris Vargaftig, Thomas Secher, Ricardo Martins Oliveira-Filho, Tatiana Victoni, René Moser, Mamdouh A. Kamal, Andressa de Freitas, Gregoire Lauvaux, Wothan Tavares-de-Lima, Bernhard Ryffel, Alexandre Learth Soares, Fernando Rodrigues Coelho, Rodrigo Guabiraba, François Erard |
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Přispěvatelé: | Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Fondation pour la Recherche Medicale (F.R.M., France), the European Community, EC (TB REACT Contract n° 028190), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (02/06606-3, 04/14128-0), Conselho Nacional de Pesquisa (CNPq) |
Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Lung Diseases
Male MESH: Histocytochemistry Neutrophils Interleukin-1beta Vascular permeability Bacteremia MESH: Neutrophils MESH: Intestinal Diseases My D88 MESH: Mice Knockout Mice MESH: Lung Diseases 0302 clinical medicine Ischemia MESH: Interleukin-1beta Immunology and Allergy MESH: Animals Receptor MESH: Bacteremia Lung Mice Knockout 0303 health sciences Mice Inbred BALB C Microscopy Histocytochemistry Toll-Like Receptors General Medicine 3. Good health Intestines Reperfusion Injury MESH: Survival Analysis [SDV.IMM]Life Sciences [q-bio]/Immunology Tumor necrosis factor alpha medicine.symptom MESH: Toll-Like Receptors MESH: Myeloid Differentiation Factor 88 MESH: Intestines Microbiology (medical) MESH: Microscopy Immunology Bacterial Toxins MESH: Mice Inbred BALB C Inflammation Lung injury Biology Capillary Permeability 03 medical and health sciences TLR medicine Animals MESH: Lung MESH: Mice 030304 developmental biology Innate immune system Bacteria Tumor Necrosis Factor-alpha lung inflammation MESH: Capillary Permeability medicine.disease Survival Analysis MESH: Male Intestinal Diseases MESH: Bacteria MESH: Bacterial Toxins intestinal ischemia MESH: Tumor Necrosis Factor-alpha Myeloid Differentiation Factor 88 MESH: Reperfusion Injury MESH: Ischemia Reperfusion injury 030215 immunology |
Zdroj: | Medical Microbiology and Immunology Medical Microbiology and Immunology, Springer Verlag, 2010, 199 (1), pp.35-42. ⟨10.1007/s00430-009-0134-5⟩ |
ISSN: | 0300-8584 1432-1831 |
Popis: | Victoni, Tatiana Coelho, Fernando Rodrigues Soares, Alexandre Learth de Freitas, Andressa Secher, Thomas Guabiraba, Rodrigo Erard, Francois de Oliveira-Filho, Ricardo Martins Vargaftig, B Boris Lauvaux, Gregoire Kamal, Mamdouh A Ryffel, Bernhard Moser, Rene Tavares-de-Lima, Wothan Germany Med Microbiol Immunol. 2010 Feb;199(1):35-42. doi: 10.1007/s00430-009-0134-5. Epub 2009 Nov 26.; International audience; Innate immune responses against microorganisms may be mediated by Toll-like receptors (TLRs). Intestinal ischemia-reperfusion (i-I/R) leads to the translocation of bacteria and/or bacterial products such as endotoxin, which activate TLRs leading to acute intestinal and lung injury and inflammation observed upon gut trauma. Here, we investigated the role of TLR activation by using mice deficient for the common TLR adaptor protein myeloid differentiation factor 88 (MyD88) on local and remote inflammation following intestinal ischemia. Balb/c and MyD88(-/-) mice were subjected to occlusion of the superior mesenteric artery (45 min) followed by intestinal reperfusion (4 h). Acute neutrophil recruitment into the intestinal wall and the lung was significantly diminished in MyD88(-/-) after i-I/R, which was confirmed microscopically. Diminished neutrophil recruitment was accompanied with reduced concentration of TNF-alpha and IL-1beta level. Furthermore, diminished microvascular leak and bacteremia were associated with enhanced survival of MyD88(-/-) mice. However, neither TNF-alpha nor IL-1beta neutralization prevented neutrophil recruitment into the lung but attenuated intestinal inflammation upon i-I/R. In conclusion, our data demonstrate that disruption of the TLR/MyD88 pathway in mice attenuates acute intestinal and lung injury, inflammation, and endothelial damage allowing enhanced survival. |
Databáze: | OpenAIRE |
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