NDLI: Pneumococci induced TLR- and Rac1-dependent NF-kappaB-recruitment to the IL-8 promoter in lung epithelial cells.

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Pneumococci induced TLR- and Rac1-dependent NF-kappaB-recruitment to the IL-8 promoter in lung epithelial cells.

Content Provider	Semantic Scholar
Author	Schmeck, Bernd Huber, Sylvia Moog, Kerstin Zahlten, Janine Hocke, Andreas Opitz, Bastian Hammerschmidt, Sven Mitchell, Tim J. Kracht, Michael Rosseau, Simone Suttorp, Norbert Hippenstiel, Stefan
Copyright Year	2006
Abstract	Streptococcus pneumoniae is the major pathogen of community-acquired pneumonia. The respiratory epithelium constitutes the first line of defense against invading lung pathogens, including pneumococci. We analyzed the involvement of Toll-like receptors (TLR) and Rho-GTPase signaling in the activation of human lung epithelial cells by pneumococci. S. pneumoniae induced release of interleukin-8 (IL-8) by human bronchial epithelial cell line BEAS-2B. Specific inhibition of Rac1 by Nsc23766 or a dominant-negative mutant of Rac1 strongly reduced cytokine release. In addition, pneumococci-related cell activation (IL-8 release, NF-kappaB-activation) depended on MyD88, phosphatidylinositol 3-kinase, and Cdc42 but not on RhoA. Pneumococci enhanced TLR1 and TLR2 mRNA expression in BEAS-2B cells, whereas TLR4 and TLR6 expression was constitutively high. TLR1 and 2 synergistically recognized pneumococci in cotransfection experiments. TLR4, TLR6, LPS-binding protein, and CD14 seem not to be involved in pneumococci-dependent cell activation. At the IL-8 gene promoter, recruitment of phosphorylated NF-kappaB subunit p65 was blocked by inhibition of Rac1, whereas binding of the phosphorylated activator protein-1 subunit c-Jun to the promoter was not diminished. In summary, these results suggest that S. pneumoniae activate human epithelial cells by TLR1/2 and a phosphatidylinositol 3-kinase- and Rac1-dependent NF-kappaB-recruitment to the IL-8 promoter.
Starting Page	L730
Ending Page	L737
Page Count	8
File Format	PDF HTM / HTML
DOI	10.1152/ajplung.00271.2005
PubMed reference number	16299055
Journal	Medline
Volume Number	290
Issue Number	4
Alternate Webpage(s)	http://ajplung.physiology.org/content/ajplung/290/4/l730.full.pdf
Alternate Webpage(s)	https://doi.org/10.1152/ajplung.00271.2005
Journal	American journal of physiology. Lung cellular and molecular physiology
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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Pneumococci induced TLR- and Rac1-dependent NF-kappaB-recruitment to the IL-8 promoter in lung epithelial cells.