Functions and Regulation of NF-κB RelA during Pneumococcal Pneumonia

摘要: Eradication of bacteria in the lower respiratory tract depends on coordinated expression proinflammatory cytokines and consequent neutrophilic inflammation. To determine roles NF-kappaB subunit RelA facilitating these events, we infected RelA-deficient mice (generated a TNFR1-deficient background) with Streptococcus pneumoniae. deficiency decreased cytokine expression, alveolar neutrophil emigration, lung bacterial killing. S. pneumoniae killing was also diminished lungs expressing dominant-negative form IkappaBalpha airway epithelial cells, implicating this cell type as an important locus activation during pneumonia. study mechanisms activation, stimulated murine line (MLE-15) bronchoalveolar lavage fluid (BALF) harvested from Pneumonic BALF, but not pneumoniae, induced degradation IkappaBbeta rapid nuclear accumulation RelA. Moreover, BALF-induced activity completely abolished following combined individual neutralization TNF IL-1 signaling, suggesting either is sufficient necessary for Our results demonstrate that essential host defense response to pneumococcus cells primarily activated by IL-1.