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

Author(s):Show less -

Victoni, Tatiana ^[1] ; Coelho, Fernando Rodrigues ^[1] ; Soares, Alexandre Learth ^[1] ; de Freitas, Andressa ^[2] ; Secher, Thomas ^{[3, 4]} ; Guabiraba, Rodrigo ^{[3, 4]} ; Erard, Francois ^{[3, 4]} ; de Oliveira-Filho, Ricardo Martins ^[1] ; Vargaftig, B. Boris ^[1] ; Lauvaux, Gregoire ^[5] ; Kamal, Mamdouh A. ^{[3, 4]} ; Ryffel, Bernhard ^{[3, 4]} ; Moser, Rene ^[6] ; Tavares-de-Lima, Wothan ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Pharmacol, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto - Brazil

^[3] CNRS, UMR6218, F-45071 Orleans - France

^[4] Univ Orleans, F-45071 Orleans 2 - France

^[5] CIML, F-13288 Marseille 09 - France

^[6] Biomed Res Fdn, CH-9548 Matzingen - Switzerland

• Document type: Journal article
• Source: MEDICAL MICROBIOLOGY AND IMMUNOLOGY; v. 199, n. 1, p. 35-42, FEB 2010.
• Web of Science Citations: 40

Abstract

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-1 beta level. Furthermore, diminished microvascular leak and bacteremia were associated with enhanced survival of MyD88(-/-) mice. However, neither TNF-alpha nor IL-1 beta 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. (AU)

• FAPESP's process: 04/14128-0 - Neuroimmunomodulation: effects of drugs, stress and cytocines on central nervous and immune systems bidirectional relationships
• Grantee: João Palermo Neto
• Support Opportunities: Research Projects - Thematic Grants