Punicic Acid a Conjugated Linolenic Acid Inhibits TNFα-Induced Neutrophil Hyperactivation and Protects from Experimental Colon Inflammation in Rats 英文参考文献.docVIP

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Punicic Acid a Conjugated Linolenic Acid Inhibits TNFα-Induced Neutrophil Hyperactivation and Protects from Experimental Colon Inflammation in Rats 英文参考文献.doc

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Punicic Acid a Conjugated Linolenic Acid Inhibits TNFα-Induced Neutrophil Hyperactivation and Protects from Experimental Colon Inflammation in Rats 英文参考文献

PunicicAcidaConjugatedLinolenicAcidInhibitsTNFa- InducedNeutrophilHyperactivationandProtectsfrom ExperimentalColonInflammationinRats TarekBoussetta1,HoussamRaad1,PhilippeLette′ron1,Marie-AnneGougerot-Pocidalo1,2 ,Jean-Claude Marie1,FathiDriss1,2,3.*,JamelEl-Benna1. * 1INSERM,U773,Universite′ Paris,Faculte′ deMe′decine,Paris,France,2AssistancePubliqueHopitauxDeParis(AP-HP),CentreHospitalo-UniversitaireXavierBichat,CIB Phenogen,Paris,France,3Universite′ deVersaillesSaintQuentinenYvelines,Versailles,France Abstract Background:NeutrophilsplayamajorroleininflammationbyreleasinglargeamountsofROSproducedbyNADPH-oxidase andmyeloperoxidase(MPO).TheproinflammatorycytokineTNFaprimesROSproductionthroughphosphorylationofthe NADPH-oxidasesubunitp47phoxonSer345.Conventionalanti-inflammatorytherapiesremainpartiallysuccessfulandmay have side effects. Therefore, regulation of neutrophil activation by natural dietary components represents an alternative therapeuticstrategyininflammatorydiseasessuchasinflammatoryboweldiseases.Theaimofthisstudywastoassessthe effect of punicic acid, a conjugated linolenic fatty acid from pomegranate seed oil on TNFa-induced neutrophil hyperactivationinvitroandoncoloninflammationinvivo. MethodologyandPrincipalFindings:WeanalyzedtheeffectofpunicicacidonTNFa-inducedneutrophilupregulationof ROS production in vitro and on TNBS-induced rat colon inflammation. Results show that punicic acid inhibited TNFa- induced priming of ROS production in vitro while preserving formyl-methionyl-leucyl-phenylalanine (fMLP)-induced response.ThiseffectwasmediatedbytheinhibitionofSer345-p47phoxphosphorylationandupstreamkinasep38MAPK. PunicicacidalsoinhibitedfMLP-andTNFa+fMLP-inducedMPOextracellularreleasefromneutrophils.Invivoexperiments showedthatpunicicacidandpomegranateseedoilintakedecreasedneutrophil-activationandROS/MPO-mediatedtissue damageasmeasuredbyF2-isoprostanereleaseandprotectedratsfromTNBS-inducedcoloninflammation. Conclusions/Significance:Thesedatashowthatpun