The Impact of Simvastatin on Pulmonary Effectors of Pseudomonas aeruginosa Infection

The statin family of cholesterol-lowering drugs is known to have pleiotropic properties which include anti-inflammatory and immunomodulatory effects. Statins exert their pleiotropic effects by altering expression of human immune regulators including pro-inflammatory cytokines. Previously we found th...

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Main Authors: Hennessy, E., O'Callaghan, J., Mooij, M., Legendre, C., Camacho-Vanegas, O., Camacho, S., Adams, C., Martignetti, J., O'Gara, Fergal
Format: Journal Article
Published: Public Library of Science 2014
Online Access:http://hdl.handle.net/20.500.11937/28253
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author Hennessy, E.
O'Callaghan, J.
Mooij, M.
Legendre, C.
Camacho-Vanegas, O.
Camacho, S.
Adams, C.
Martignetti, J.
O'Gara, Fergal
author_facet Hennessy, E.
O'Callaghan, J.
Mooij, M.
Legendre, C.
Camacho-Vanegas, O.
Camacho, S.
Adams, C.
Martignetti, J.
O'Gara, Fergal
author_sort Hennessy, E.
building Curtin Institutional Repository
collection Online Access
description The statin family of cholesterol-lowering drugs is known to have pleiotropic properties which include anti-inflammatory and immunomodulatory effects. Statins exert their pleiotropic effects by altering expression of human immune regulators including pro-inflammatory cytokines. Previously we found that statins modulate virulence phenotypes of the human pathogen Pseudomonas aeruginosa, and sought to investigate if simvastatin could alter the host response to this organism in lung epithelial cells. Simvastatin increased the expression of the P. aeruginosa target genes KLF2, KLF6, IL-8 and CCL20.Furthermore, both simvastatin and P. aeruginosa induced alternative splicing of KLF6. The novel effect of simvastatin on wtKLF6 expression was found to be responsible for induction of the KLF6 regulated genes CCL20 and iNOS. Simvastatin also increased the adhesion of P. aeruginosa to host cells, without altering invasion or cytotoxicity. This study demonstrated that simvastatin had several novel effects on the pulmonary cellular immune response.
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spelling curtin-20.500.11937-282532017-09-13T15:21:25Z The Impact of Simvastatin on Pulmonary Effectors of Pseudomonas aeruginosa Infection Hennessy, E. O'Callaghan, J. Mooij, M. Legendre, C. Camacho-Vanegas, O. Camacho, S. Adams, C. Martignetti, J. O'Gara, Fergal The statin family of cholesterol-lowering drugs is known to have pleiotropic properties which include anti-inflammatory and immunomodulatory effects. Statins exert their pleiotropic effects by altering expression of human immune regulators including pro-inflammatory cytokines. Previously we found that statins modulate virulence phenotypes of the human pathogen Pseudomonas aeruginosa, and sought to investigate if simvastatin could alter the host response to this organism in lung epithelial cells. Simvastatin increased the expression of the P. aeruginosa target genes KLF2, KLF6, IL-8 and CCL20.Furthermore, both simvastatin and P. aeruginosa induced alternative splicing of KLF6. The novel effect of simvastatin on wtKLF6 expression was found to be responsible for induction of the KLF6 regulated genes CCL20 and iNOS. Simvastatin also increased the adhesion of P. aeruginosa to host cells, without altering invasion or cytotoxicity. This study demonstrated that simvastatin had several novel effects on the pulmonary cellular immune response. 2014 Journal Article http://hdl.handle.net/20.500.11937/28253 10.1371/journal.pone.0102200 Public Library of Science unknown
spellingShingle Hennessy, E.
O'Callaghan, J.
Mooij, M.
Legendre, C.
Camacho-Vanegas, O.
Camacho, S.
Adams, C.
Martignetti, J.
O'Gara, Fergal
The Impact of Simvastatin on Pulmonary Effectors of Pseudomonas aeruginosa Infection
title The Impact of Simvastatin on Pulmonary Effectors of Pseudomonas aeruginosa Infection
title_full The Impact of Simvastatin on Pulmonary Effectors of Pseudomonas aeruginosa Infection
title_fullStr The Impact of Simvastatin on Pulmonary Effectors of Pseudomonas aeruginosa Infection
title_full_unstemmed The Impact of Simvastatin on Pulmonary Effectors of Pseudomonas aeruginosa Infection
title_short The Impact of Simvastatin on Pulmonary Effectors of Pseudomonas aeruginosa Infection
title_sort impact of simvastatin on pulmonary effectors of pseudomonas aeruginosa infection
url http://hdl.handle.net/20.500.11937/28253