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dc.contributor.authorA. Cooley, Margaret
dc.contributor.authorWhittall, Christine
dc.contributor.authorS. Rolph, Michael
dc.date.accessioned2017-05-03T16:02:13Z
dc.date.available2017-05-03T16:02:13Z
dc.date.issued2010
dc.date.modified2011-03-23T05:46:42Z
dc.identifier.issn12864579
dc.identifier.doi10.1016/j.micinf.2009.12.009
dc.identifier.urihttp://hdl.handle.net/10072/37636
dc.description.abstractPeroxisome proliferator activated receptor (PPARγ) has been suggested as a target for anti-inflammatory therapy in chronic lung disease, including infection with Pseudomonas aeruginosa. However, the P. aeruginosa signal molecule N-(3-oxo-dodecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) has been reported to inhibit function of PPARs in mammalian cells. This suggests that binding of 3-oxo-C12-HSL to PPARs could increase inflammation during P. aeruginosa infection, particularly if it could compete for binding with other PPAR ligands. We investigated the ability of 3-oxo-C12-HSL to bind to a PPAR? ligand binding domain (LBD) construct, and to compete for binding with the highly active synthetic PPARγ agonist rosiglitazone. We demonstrate that 3-oxo-C12-HSL binds effectively to the PPARγ ligand binding domain, and that concentrations of 3-oxo-C12-HSL as low as 1 nM can effectively interfere with the binding of rosiglitazone to the PPARγ ligand binding domain. Because 3-oxo-C12 HSL has been demonstrated in lungs during P. aeruginosa infection, blockade of PPARγ-dependent signaling by 3-oxo-C12-HSL produced by the infecting P. aeruginosa could exacerbate infection-associated inflammation, and potentially impair the action of PPAR-activating therapy. Thus the proposed use of PPARγ agonists as anti-inflammatory therapy in lung P. aeruginosa infection may depend on their ability to counteract the effects of 3-oxo-C12-HSL.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.publisher.placeFrance
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom231
dc.relation.ispartofpageto237
dc.relation.ispartofissue3
dc.relation.ispartofjournalMicrobes and Infection
dc.relation.ispartofvolume12
dc.rights.retentionY
dc.subject.fieldofresearchBacteriology
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchcode060501
dc.subject.fieldofresearchcode0605
dc.subject.fieldofresearchcode1107
dc.subject.fieldofresearchcode1108
dc.titlePseudomonas signal molecule 3-oxo-c12-homoserine lactone interferes with binding of rosiglitazone to human PPARγ
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2010
gro.hasfulltextNo Full Text
gro.griffith.authorRolph, Michael S.


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