| pubmed-article:20650996 | pubmed:abstractText | Severe community- and hospital-acquired pneumonia is caused by Legionella pneumophila. Lung airway and alveolar epithelial cells comprise an important sentinel system in airborne infections. Although interleukin (IL)-6 is known as a central regulator of the immune response in pneumonia, its regulation in the lung is widely unknown. Herein, we demonstrate that different L. pneumophila strains induce delayed expression of IL-6 in comparison with IL-8 by human lung epithelial cells. IL-6 expression depended, at early time points, on flagellin recognition by Toll-like receptor (TLR)5, activity of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)1 and p38 mitogen-activated protein (MAP) kinase, and, at later time points, on the type-IV secretion system. In the same manner, but more rapidly, the recently described transcription factor I?B? was induced by Legionella infection and, binding to the nuclear factor (NF)-?B subunit p50 - recruited to the il6 promoter together with CCAAT-enhancer-binding protein ? and phosphorylated activator protein-1 subunit cJun. Similarly, histone modifications and NF-?B subunit p65/RelA appeared at the i?b? and subsequently at the il6 gene promoter, thereby initiating gene expression. Gene silencing of I?B? reduced Legionella-related IL-6 expression by 41%. Overall, these data indicate a sequence of flagellin/TLR5- and type IV-dependent I?B? expression, recruitment of I?B?/p50 to the il6 promoter, chromatin remodelling and subsequent IL-6 transcription in L. pneumophila-infected lung epithelial cells. | lld:pubmed |
