title: The impact of simvastatin on pulmonary effectors of Pseudomonas aeruginosa infection.
abstract: 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.
authors.affiliation: BIOMERIT Research Centre, School of Microbiology, National University of Ireland, Cork, Ireland.
authors.forename: Emma
authors.initials: E
authors.lastname: Hennessy
authors.affiliation: BIOMERIT Research Centre, School of Microbiology, National University of Ireland, Cork, Ireland.
authors.forename: Julie
authors.initials: J
authors.lastname: O'Callaghan
authors.affiliation: BIOMERIT Research Centre, School of Microbiology, National University of Ireland, Cork, Ireland.
authors.forename: Marlies J
authors.initials: MJ
authors.lastname: Mooij
authors.affiliation: BIOMERIT Research Centre, School of Microbiology, National University of Ireland, Cork, Ireland.
authors.forename: Claire
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Olga
authors.initials: O
authors.lastname: Camacho-Vanegas
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Camacho
authors.affiliation: BIOMERIT Research Centre, School of Microbiology, National University of Ireland, Cork, Ireland.
authors.forename: Claire
authors.initials: C
authors.lastname: Adams
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: Martignetti
authors.affiliation: BIOMERIT Research Centre, School of Microbiology, National University of Ireland, Cork, Ireland; School of Biomedical Sciences, Curtin University, Perth, WA, Australia.
authors.forename: Fergal
authors.initials: F
authors.lastname: O'Gara
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects; D002460:Cell Line; D054418:Chemokine CCL20 / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D016209:Interleukin-8 / Q000096:biosynthesis; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity; D019821:Simvastatin / Q000008:administration & dosage*
chemical_list: C108355:CCL20 protein, human; D054418:Chemokine CCL20; D016209:Interleukin-8; C096161:KLF2 protein, human; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D019821:Simvastatin