Chemokine Expression in Inflamed Adipose Tissue Is Mainly Mediated by NF-κB.docVIP

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Chemokine Expression in Inflamed Adipose Tissue Is Mainly Mediated by NF-κB.doc

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Chemokine Expression in Inflamed Adipose Tissue Is Mainly Mediated by NF-κB

ChemokineExpressioninInflamedAdiposeTissueIs MainlyMediatedbyNF-kB FranckTourniaire1,2,3,BeatriceRomier-Crouzet1,2,3,JongHanLee4,JulieMarcotorchino1,2,3, ErwanGouranton1,2,3,JeromeSalles5,ChristianeMalezet1,2,3,JulienAstier1,2,3,PatriceDarmon1,2,3 EricBlouin6,StephaneWalrand5,JianpingYe4,Jean-FrancoisLandrier1,2,3* , 1INRA, UMR 1260, Marseille, France, 2INSERM, UMR 1062, ? Nutrition, Obe′site′ et Risque Thrombotique ?, Marseille, France, 3Universite′ d’Aix-Marseille, Faculte′ de Me′decine,Marseille,France,4PenningtonBiomedicalResearchCenter,LouisianaStateUniversitySystem,BatonRouge,Louisiana,UnitedStatesofAmerica,5UMRINRA 1019Unite′ denutritionhumaine,CentredeRecherchesINRAdeClermont-Ferrand/Theix,StGene`s Champanelle,France,6LaboratoireLabcatal,Montrouge,France Abstract Immunecellinfiltrationofexpandingadiposetissueduringobesityanditsroleininsulinresistancehasbeendescribedand involveschemokines.However,studiessofarhavefocusedonasinglechemokineoritsreceptor(especiallyCCL2andCCL5) whereasredundantfunctionsofchemokineshavebeendescribed.Theobjectiveofthisworkwastoexploretheexpression of chemokines in inflamed adipose tissue in obesity. Human and mouse adipocytes were analyzed for expression of chemokines in response to inflammatory signal (TNF-a) using microarrays and gene set enrichment analysis. Gene expression was verified by qRT-PCR. Chemokine protein was determined in culture medium with ELISA. Chemokine expressionwasinvestigatedinhumansubcutaneousadiposetissuebiopsiesandmechanismofchemokineexpressionwas investigated using chemical inhibitors and cellular and animal transgenic models. Chemokine encoding genes were the mostresponsivegenesinTNF-atreatedhumanandmouseadipocytes.mRNAandproteinof34chemokinegeneswere inducedinadose-dependentmannerintheculturesystem.Furthermore,expressionofthosechemokineswaselevatedin human obese adipose tissue. Finally, chemokine expression was reduced by NF-kB inactivation and elevated by NF-kB activation. Our data indicate that