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Functions and Regulation of NF-B RelA during Pneumococcal Pneumonia 1
| Content Provider | Semantic Scholar |
|---|---|
| Author | Quinton, Lee J. Jones, Matthew R. Simms, Benjamin T. Kogan, Mariya S. Robson, Bryanne E. Skerrett, Shawn J. Mizgerd, Joseph P. |
| Copyright Year | 2007 |
| Abstract | Eradication of bacteria in the lower respiratory tract depends on the coordinated expression of proinflammatory cytokines and consequent neutrophilic inflammation. To determine the roles of the NFB subunit RelA in facilitating these events, we infected RelA-deficient mice (generated on a TNFR1-deficient background) with Streptococcus pneumoniae. RelA deficiency decreased cytokine expression, alveolar neutrophil emigration, and lung bacterial killing. S. pneumoniae killing was also diminished in the lungs of mice expressing a dominant-negative form of I B in airway epithelial cells, implicating this cell type as an important locus of NFB activation during pneumonia. To study mechanisms of epithelial RelA activation, we stimulated a murine alveolar epithelial cell line (MLE-15) with bronchoalveolar lavage fluid (BALF) harvested from mice infected with S. pneumoniae. Pneumonic BALF, but not S. pneumoniae, induced degradation of I B and I B and rapid nuclear accumulation of RelA. Moreover, BALF-induced RelA activity was completely abolished following combined but not individual neutralization of TNF and IL-1 signaling, suggesting either cytokine is sufficient and necessary for alveolar epithelial RelA activation during pneumonia. Our results demonstrate that RelA is essential for the host defense response to pneumococcus in the lungs and that RelA in airway epithelial cells is primarily activated by TNF and IL-1. The Journal of Immunology, 2007, 178: 1896–1903. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.bumc.bu.edu/pulmonary/files/2009/09/functions.pdf |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Alveolar Epithelial Cells Angular defect Bronchoalveolar Lavage Fluid Elegant degradation Irrigation LOCUS NF-kappa B Neurofeedback Neutralization (Chemistry) RELA protein, human Respiratory Tract Diseases Respiratory tract structure Sacroiliitis Streptococcal pneumonia Streptococcus pneumoniae Structure of parenchyma of lung Tract (literature) Tree accumulation cytokine defense response host defense neutrophil |
| Content Type | Text |
| Resource Type | Article |
