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Title: STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Authors: Szanto, A
Balint, BL
Nagy, ZS
Barta, E
Dezso, B
Pap, A
Szeles, L
Poliska, S
Oros, M
Evans, RM
Barak, Y
Schwabe, J
Nagy, L
First Published: 24-Nov-2010
Citation: IMMUNITY, 2010, 33 (5), pp. 699-712
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.
DOI Link: 10.1016/j.immuni.2010.11.009
eISSN: 1097-4180
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Biochemistry

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