| Literature DB >> 30566880 |
David E Sanin1, Mai Matsushita1, Ramon I Klein Geltink1, Katarzyna M Grzes1, Nikki van Teijlingen Bakker2, Mauro Corrado1, Agnieszka M Kabat1, Michael D Buck1, Jing Qiu1, Simon J Lawless1, Alanna M Cameron1, Matteo Villa1, Francesc Baixauli1, Annette E Patterson1, Fabian Hässler1, Jonathan D Curtis1, Christina M O'Neill3, David O'Sullivan1, Duojiao Wu4, Gerhard Mittler5, Stanley Ching-Cheng Huang3, Erika L Pearce1, Edward J Pearce6.
Abstract
Metabolic engagement is intrinsic to immune cell function. Prostaglandin E2 (PGE2) has been shown to modulate macrophage activation, yet how PGE2 might affect metabolism is unclear. Here, we show that PGE2 caused mitochondrial membrane potential (Δψm) to dissipate in interleukin-4-activated (M(IL-4)) macrophages. Effects on Δψm were a consequence of PGE2-initiated transcriptional regulation of genes, particularly Got1, in the malate-aspartate shuttle (MAS). Reduced Δψm caused alterations in the expression of 126 voltage-regulated genes (VRGs), including those encoding resistin-like molecule α (RELMα), a key marker of M(IL-4) cells, and genes that regulate the cell cycle. The transcription factor ETS variant 1 (ETV1) played a role in the regulation of 38% of the VRGs. These results reveal ETV1 as a Δψm-sensitive transcription factor and Δψm as a mediator of mitochondrial-directed nuclear gene expression.Entities:
Keywords: ETS variant 1; ETV1; IL-4; PGE2; RELMα; immunometabolism; interleukin-4; macrophage; malate-aspartate shuttle; mitochondria; mitochondrial membrane potential; proliferation; prostaglandin E2
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Year: 2018 PMID： 30566880 PMCID： PMC7271981 DOI： 10.1016/j.immuni.2018.10.011
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745