RGD Reference Report - Local and remote tissue injury upon intestinal ischemia and reperfusion depends on the TLR/MyD88 signaling pathway. - Rat Genome Database

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Local and remote tissue injury upon intestinal ischemia and reperfusion depends on the TLR/MyD88 signaling pathway.

Authors: Victoni, T  Coelho, FR  Soares, AL  De Freitas, A  Secher, T  Guabiraba, R  Erard, F  De Oliveira-Filho, RM  Vargaftig, BB  Lauvaux, G  Kamal, MA  Ryffel, B  Moser, R  Tavares-de-Lima, W 
Citation: Victoni T, etal., Med Microbiol Immunol. 2010 Feb;199(1):35-42. Epub 2009 Nov 26.
RGD ID: 4142814
Pubmed: PMID:19941004   (View Abstract at PubMed)
DOI: DOI:10.1007/s00430-009-0134-5   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung disease  ISOIl1b (Mus musculus)4142814; 4142814associated with Reperfusion Injury and protein:increased expression:lungRGD 
lung disease  IEP 4142814associated with Reperfusion Injury and protein:increased expression:lungRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1b  (interleukin 1 beta)

Genes (Mus musculus)
Il1b  (interleukin 1 beta)

Genes (Homo sapiens)
IL1B  (interleukin 1 beta)


Additional Information