Legionella pneumophila-induced IκBζ-dependent expression of interleukin-6 in lung epithelium

The European Respiratory Journal
J LorenzBernd Schmeck

Abstract

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 IκBζ was induced by Legionella infection and, binding to the nuclear factor (NF)-κB subunit p50 - recruited to the il6 promoter together with CCAAT-enhancer-binding protein β and phosphorylated activator protein-1 subunit cJun. Similarly, histone modifications and NF-κB subunit p65/RelA appeared at the iκbζ and subsequently at the il6 gene promoter, thereby initiating g...Continue Reading

Citations

Jan 21, 2012·Canadian Journal of Microbiology·Yoshitomo MorinagaShimeru Kamihira
Nov 3, 2011·The Journal of Endocrinology·Abraham B Roos, Magnus Nord
Mar 9, 2011·Infection and Immunity·Kessler McCoy-SimandleNicholas P Cianciotto
Nov 6, 2018·Medical Microbiology and Immunology·Changle WangMei Liang
Jan 28, 2021·International Journal of Molecular Sciences·Laura Kate GadanecVasso Apostolopoulos

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