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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-3-1
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1399-3003
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
648-57
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Legionella pneumophila-induced I?B?-dependent expression of interleukin-6 in lung epithelium.
pubmed:affiliation
Dept of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't