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dc.contributor.authorA. Cooley, Margareten_US
dc.contributor.authorWhittall, Christineen_US
dc.contributor.authorS. Rolph, Michaelen_US
dc.date.accessioned2017-04-24T13:39:41Z
dc.date.available2017-04-24T13:39:41Z
dc.date.issued2010en_US
dc.date.modified2011-03-23T05:46:42Z
dc.identifier.issn12864579en_US
dc.identifier.doi10.1016/j.micinf.2009.12.009en_AU
dc.identifier.urihttp://hdl.handle.net/10072/37636
dc.description.abstractPeroxisome proliferator activated receptor (PPAR?) 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 PPAR? agonist rosiglitazone. We demonstrate that 3-oxo-C12-HSL binds effectively to the PPAR? 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 PPAR? ligand binding domain. Because 3-oxo-C12 HSL has been demonstrated in lungs during P. aeruginosa infection, blockade of PPAR?-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 PPAR? agonists as anti-inflammatory therapy in lung P. aeruginosa infection may depend on their ability to counteract the effects of 3-oxo-C12-HSL.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherElsevieren_US
dc.publisher.placeFranceen_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom231en_US
dc.relation.ispartofpageto237en_US
dc.relation.ispartofissue3en_US
dc.relation.ispartofjournalMicrobes and Infectionen_US
dc.relation.ispartofvolume12en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchBacteriologyen_US
dc.subject.fieldofresearchcode060501en_US
dc.titlePseudomonas signal molecule 3-oxo-c12-homoserine lactone interferes with binding of rosiglitazone to human PPARγen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.date.issued2010
gro.hasfulltextNo Full Text


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