Activation of NF-κB via a Src-dependent Ras-MAPK-pp90rsk pathway is required for Pseudomonas aeruginosa-induced mucin overproduction in epithelial cells

摘要

Cystic fibrosis (CF) is an autosomal reces- sive disorder, the most common lethal genetic disease in Caucasians. Respiratory disease is the major cause of mor- bidity and mortality. Indeed, 95/100 of CF patients die of respiratory failure. Pseudomonas aeruginosa, an opportunistic pathogen, chronically infects the lungs of over 85/100 of CF patients. It is ineradicable by antibiotics and responsible for airway mucus overproduction that contributes to airway obstruction and death. The molecular mechanisms underlying this pathology are unknown. Here we show that P. aeruginosa activates a c-Src-Ras-MEK1/2-MAPK-pp90rsk signaling pathway that leads to activation of nuclear factor NF-κB (p65/p50).