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[ Article ] Docosahexaenoic acid modulates the expression of T-bet and GATA-3 transcription factors, independently of PPARα, through suppressionof MAP kinase activation

Date de soumission: 28-03-2017
Année de Publication: 2009
Entité/Laboratoire Autres laboratoires
Document type : Article
Discipline(s) : Biochimie, biophysique & Biologie Moléculaire
Titre Docosahexaenoic acid modulates the expression of T-bet and GATA-3 transcription factors, independently of PPARα, through suppressionof MAP kinase activation
Auteurs Attakpa Sèlidji Eugène [1], Hichami Aziz [2], Simonin Anne Marie [3], Garcıa Sanson Esther [4], Dramane Karim L [5], Khan Naim Akhtar [6],
Journal: Biochimie
Catégorie Journal: Internationale
Impact factor: 3.897
Volume Journal: 91
DOI: Doi:10.1016/j.biochi.2009.09.012
Resume The present study was conducted on CD4+ Tcells, isolated fromwild type (WT) and PPARαnull mice, in order to assess the mechanism of action of do-cosahexaenoic acid (DHA), an n-3 fatty acid, in the modulation of two tran-scription factors, i.e., T-bet and GATA-3, implicated in T-cell differentiation towards, respectively, TH1 and TH2 phenotype. The T-cells from P PPARαnull mice secreted higher IFN-γ and lower IL-4 concentrations than WT T-cells. Furthermore, the deletion of PPARa gene in T-cells resulted in the upregulation of T-bet and downregulation of GATA-3 both at mRNA and protein levels. DHA exerted not only an inhibitory effect on T-cell pro-liferation, but also diminished IFN-γ and stimulated IL-4 secretions in both cell types. DHA also downregulated T-bet and u regulated GATA-3 both at transcription and protein levels. Though the T-cells from PPARαnull mice ex-pressed higher p38 phosphorylation than WT T-cells, DHA diminished the MAP kinase phosphorylation (p38 and ERK1/2) in both the cell types. The pharmacological inhibitors of MAP kinases also downregulated T-bet and upregulated GATA-3 in T-cells. Altogether, these results demonstrate that DHA, via its action on MAP kinases, modulates the expression of transcrip-tion factors. These results also explain the mechanism of action of this fatty acid on T-cell differentiation in disease and health.
Mots clés Fatty acids.T-cells. MAPK. Mouse. PPAR
Pages 1359 - 1365
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