Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen, which is the major cause of severe
chronic lung infection in cystic fibrosis patients. It is also responsible for systemic infections in immunocompromised
individuals and those presenting with significant pulmonary conditions in intensive care units. This microorganism has the
capacity to initiate severe inflammation in infected lungs resulting in detrimental tissue damage. We have hypothesized
that Syk protein tyrosine kinase mediates lung epithelial cellular responses to P. aeruginosa infection, and that a naturally
occurring non-toxic Syk inhibitor piceatannol can protect infected human cells against the deleterious effects associated
with this infection. We infected Syk-positive H292 or Syk-negative A549 human lung epithelial cell lines with P.
aeruginosa and assessed the resulting cellular responses, i.e. production of proinflammatory cytokines, adhesion molecule
expression, generation of reactive oxygen species, and apoptosis of infected cells, utilizing a multiplex bead-based
immunoassay and flow cytometry. We also studied the internalization of P. aeruginosa using the gentamicin exclusion
assay. We found that the piceatannol treatment significantly suppressed inflammation, oxidative stress and apoptosis in
H292, but not in A549 cells implicating Syk participation in the regulation of the pathological processes induced by P.
aeruginosa infection. Intriguingly, piceatannol was able to down-regulate the internalization of P. aeruginosa by both
Syk-positive and Syk-negative cell lines, implying that the mechanisms of action of this compound extend beyond Syk
inhibition. As piceatannol can interfere with several mechanisms of bacterial pathogenesis this natural compound deserves
further study as a potential therapeutic option in P. aeruginosa infection.
Keywords: Apoptosis, inflammation, lung epithelial cells, piceatannol, Pseudomonas aeruginosa, reactive oxygen species
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