Mechanical Ventilation Modulates TLR4 and IRAK-3 in a Non-infectious, Ventilator-induced Lung Injury Model
Cabrera, Nuria E
Slutsky, Arthur S
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CitationVillar, Jesús, Nuria E. Cabrera, Milena Casula, Carlos Flores, Francisco Valladares, Lucio Díaz-Flores, Mercedes Muros, Arthur S. Slutsky, and Robert M. Kacmarek. 2010. Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious, ventilator-induced lung injury model. Respiratory Research 11(1): 27.
AbstractBackground: Previous experimental studies have shown that injurious mechanical ventilation has a direct effect on pulmonary and systemic immune responses. How these responses are propagated or attenuated is a matter of speculation. The goal of this study was to determine the contribution of mechanical ventilation in the regulation of Toll-like receptor (TLR) signaling and interleukin-1 receptor associated kinase-3 (IRAK-3) during experimental ventilator-induced lung injury. Methods: Prospective, randomized, controlled animal study using male, healthy adults Sprague-Dawley rats weighing 300-350 g. Animals were anesthetized and randomized to spontaneous breathing and to two different mechanical ventilation strategies for 4 hours: high tidal volume (VT) (20 ml/kg) and low VT (6 ml/kg). Histological evaluation, TLR2, TLR4, IRAK3 gene expression, IRAK-3 protein levels, inhibitory kappa B alpha (IκBα), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL6) gene expression in the lungs and TNF-α and IL-6 protein serum concentrations were analyzed. Results: High VT mechanical ventilation for 4 hours was associated with a significant increase of TLR4 but not TLR2, a significant decrease of IRAK3 lung gene expression and protein levels, a significant decrease of IκBα, and a higher lung expression and serum concentrations of pro-inflammatory cytokines. Conclusions: The current study supports an interaction between TLR4 and IRAK-3 signaling pathway for the over-expression and release of pro-inflammatory cytokines during ventilator-induced lung injury. Our study also suggests that injurious mechanical ventilation may elicit an immune response that is similar to that observed during infections.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5978760
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