title: STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
abstract: Peroxisome proliferator-activated receptor γ (PPARγ) is a lipid-activated transcription factor regulating lipid metabolism and inflammatory response in macrophages and dendritic cells (DCs). These immune cells exposed to distinct inflammatory milieu show cell type specification as a result of altered gene expression. We demonstrate here a mechanism how inflammatory molecules modulate PPARγ signaling in distinct subsets of cells. Proinflammatory molecules inhibited whereas interleukin-4 (IL-4) stimulated PPARγ activity in macrophages and DCs. Furthermore, IL-4 signaling augmented PPARγ activity through an interaction between PPARγ and signal transducer and activators of transcription 6 (STAT6) on promoters of PPARγ target genes, including FABP4. Thus, STAT6 acts as a facilitating factor for PPARγ by promoting DNA binding and consequently increasing the number of regulated genes and the magnitude of responses. This interaction, underpinning cell type-specific responses, represents a unique way of controlling nuclear receptor signaling by inflammatory molecules in immune cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Egyetem ter 1. Debrecen, H-4010, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Szanto
authors.forename: Balint L
authors.initials: BL
authors.lastname: Balint
authors.forename: Zsuzsanna S
authors.initials: ZS
authors.lastname: Nagy
authors.forename: Endre
authors.initials: E
authors.lastname: Barta
authors.forename: Balazs
authors.initials: B
authors.lastname: Dezso
authors.forename: Attila
authors.initials: A
authors.lastname: Pap
authors.forename: Lajos
authors.initials: L
authors.lastname: Szeles
authors.forename: Szilard
authors.initials: S
authors.lastname: Poliska
authors.forename: Melinda
authors.initials: M
authors.lastname: Oros
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Barak
authors.forename: John
authors.initials: J
authors.lastname: Schwabe
authors.forename: Laszlo
authors.initials: L
authors.lastname: Nagy
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D050800:STAT6 Transcription Factor / Q000378:metabolism*
chemical_list: C493410:FABP4 protein, human; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D018836:Inflammation Mediators; D047495:PPAR gamma; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C494100:Stat6 protein, mouse; D015847:Interleukin-4