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Endotoxin/TLR3 signal transduction pathway: role in lung injury

 
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doi: 10.18081/2333-5106/015-06/333-344
American Journal of BioMedicine Volume 3, Issue 6, pages 333-344
Published: June 25, 2015


Mariana B. Friedman, Halley A. Schmid, Astor S. Josef, Mark Longton

Abstract

Toll-like receptor 3 (TLR3) recognize extracellular RNA (exRNA) released from lung diseases of immune origin but the pathogenesis remain little described in endotoxin lung injury. We investigated the expression and function of TLR3 in peripheral blood mononuclear cells (PBMC) of endotoxin lung injury. TLR3(-/-) and wild-type (WT) mice were exposed to to 1 hr of left lung warm ischemia followed by 6 hr of reperfusion. We found that TLR3(-/-) mice had significantly reduced AKT phosphorylation and markedly decreased the expression of proinflammatory chemokine/cytokine levels and neutrophil recruitment in the left lung following ischemia-reperfusion as compared with wildtype mice. These results indicate that endotoxin functions as a differential regulator of TLR3 signaling pathways by facilitating TLR3 endocytic trafficking in monocytes in the lung inflammatory response to endotoxin.

Keywords: TLR3; AKT phosphorylation; proinflammatory cytokine; Lung injury


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