Kinase activity profiling of pneumococcal pneumonia.

<h4>Background</h4>Pneumonia represents a major health burden. Previous work demonstrated that although the induction of inflammation is important for adequate host defense against pneumonia, an inability to regulate the host's inflammatory response within the lung later during infe...

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Autores principales:	Arie J Hoogendijk, Sander H Diks, Tom van der Poll, Maikel P Peppelenbosch, Catharina W Wieland
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b42593a1cb3d4abe8ab8aa22bd22f79d
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spelling	oai:doaj.org-article:b42593a1cb3d4abe8ab8aa22bd22f79d2021-11-18T06:56:14ZKinase activity profiling of pneumococcal pneumonia.1932-620310.1371/journal.pone.0018519https://doaj.org/article/b42593a1cb3d4abe8ab8aa22bd22f79d2011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21483672/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Pneumonia represents a major health burden. Previous work demonstrated that although the induction of inflammation is important for adequate host defense against pneumonia, an inability to regulate the host's inflammatory response within the lung later during infection can be detrimental. Intracellular signaling pathways commonly rely on activation of kinases, and kinases play an essential role in the regulation of the inflammatory response of immune cells.<h4>Methodology/principal findings</h4>Pneumonia was induced in mice via intranasal instillation of Streptococcus (S.) pneumoniae. Kinomics peptide arrays, exhibiting 1024 specific consensus sequences for protein kinases, were used to produce a systems biology analysis of cellular kinase activity during the course of pneumonia. Several differences in kinase activity revealed by the arrays were validated in lung homogenates of individual mice using western blot. We identified cascades of activated kinases showing that chemotoxic stress and a T helper 1 response were induced during the course of pneumococcal pneumonia. In addition, our data point to a reduction in WNT activity in lungs of S. pneumoniae infected mice. Moreover, this study demonstrated a reduction in overall CDK activity implying alterations in cell cycle biology.<h4>Conclusions/significance</h4>This study utilizes systems biology to provide insight into the signaling events occurring during lung infection with the common cause of community acquired pneumonia, and may assist in identifying novel therapeutic targets in the treatment of bacterial pneumonia.Arie J HoogendijkSander H DiksTom van der PollMaikel P PeppelenboschCatharina W WielandPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e18519 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arie J Hoogendijk Sander H Diks Tom van der Poll Maikel P Peppelenbosch Catharina W Wieland Kinase activity profiling of pneumococcal pneumonia.
description	<h4>Background</h4>Pneumonia represents a major health burden. Previous work demonstrated that although the induction of inflammation is important for adequate host defense against pneumonia, an inability to regulate the host's inflammatory response within the lung later during infection can be detrimental. Intracellular signaling pathways commonly rely on activation of kinases, and kinases play an essential role in the regulation of the inflammatory response of immune cells.<h4>Methodology/principal findings</h4>Pneumonia was induced in mice via intranasal instillation of Streptococcus (S.) pneumoniae. Kinomics peptide arrays, exhibiting 1024 specific consensus sequences for protein kinases, were used to produce a systems biology analysis of cellular kinase activity during the course of pneumonia. Several differences in kinase activity revealed by the arrays were validated in lung homogenates of individual mice using western blot. We identified cascades of activated kinases showing that chemotoxic stress and a T helper 1 response were induced during the course of pneumococcal pneumonia. In addition, our data point to a reduction in WNT activity in lungs of S. pneumoniae infected mice. Moreover, this study demonstrated a reduction in overall CDK activity implying alterations in cell cycle biology.<h4>Conclusions/significance</h4>This study utilizes systems biology to provide insight into the signaling events occurring during lung infection with the common cause of community acquired pneumonia, and may assist in identifying novel therapeutic targets in the treatment of bacterial pneumonia.
format	article
author	Arie J Hoogendijk Sander H Diks Tom van der Poll Maikel P Peppelenbosch Catharina W Wieland
author_facet	Arie J Hoogendijk Sander H Diks Tom van der Poll Maikel P Peppelenbosch Catharina W Wieland
author_sort	Arie J Hoogendijk
title	Kinase activity profiling of pneumococcal pneumonia.
title_short	Kinase activity profiling of pneumococcal pneumonia.
title_full	Kinase activity profiling of pneumococcal pneumonia.
title_fullStr	Kinase activity profiling of pneumococcal pneumonia.
title_full_unstemmed	Kinase activity profiling of pneumococcal pneumonia.
title_sort	kinase activity profiling of pneumococcal pneumonia.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b42593a1cb3d4abe8ab8aa22bd22f79d
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Kinase activity profiling of pneumococcal pneumonia.

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