Alpha-tocopherol Attenuates the Severity of Pseudomonas aeruginosa-induced Pneumonia.

Alpha-tocopherol Attenuates the Severity of Pseudomonas aeruginosa-induced Pneumonia. Am J Respir Cell Mol Biol. 2020 Apr 03;: Authors: Wagener BM, Anjum N, Evans C, Brandon A, Honavar J, Creighton J, Traber MG, Stuart RL, Stevens T, Pittet JF Abstract Pseudomonas aeruginosa is a lethal pathogen that causes high mortality and morbidity in immunocompromised and critically ill patients. The Type III secretion system (T3SS) of P. aeruginosa mediates many of the adverse effects of infection with this pathogen including increased lung permeability in a toll-like receptor 4/Rho A/plasminogen activator inhibitor (PAI)-1-dependent manner. Alpha-tocopherol has anti-inflammatory properties that may make it a useful adjunct in treatment of this moribund infection. We measured transendothelial and transepithelial resistance, Rho A and PAI-1 activation, stress fiber formation, P. aeruginosa T3SS exoenzyme (Exo Y) intoxication into host cells, and survival in a murine model of pneumonia in the presence of P. aeruginosa and pretreatment with α-tocopherol. We found that α-tocopherol alleviated P. aeruginosa-mediated alveolar endothelial and epithelial paracellular permeability by inhibiting RhoA, in part, via PAI-1 activation and increased survival in a mouse model of P. aeruginosa pneumonia. Furthermore, we found that α-tocopherol decreased the activation of RhoA and PAI-1 by blocking the injection of T3SS exoenzymes into alveolar epithelial cel...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research