EP4-Tg aortic VSMCs: Control vs PGE2
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ABSTRACT:
PROVIDER: PRJNA611821 | ENA |
REPOSITORIES: ENA
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Project description:RNA sequencing was used to determine the impact of PGE2 signaling on NK cell function. Our analysis revealed that PGE2 induces a dysfunctional program in NK cells characterized by the inability to produce cytokines and chemokines upon their activation. Mechanistically, this program is governed by transcriptional changes downstream of the PGE2 receptors EP2 and EP4.
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Project description:A persistent and non-resolving inflammatory response to accumulating A? peptide species is a cardinal feature in the development of Alzheimer's disease (AD). In response to accumulating A? peptide species, microglia, the innate immune cells of the brain, generate a toxic inflammatory response that accelerates synaptic and neuronal injury. Many pro-inflammatory signaling pathways are linked to progression of neurodegeneration. However, endogenous anti-inflammatory pathways capable of suppressing A?-induced inflammation represent a relatively unexplored area. Here we hypothesized that signaling through the prostaglandin-E2 (PGE2) EP4 receptor potently suppresses microglial inflammatory responses to A?42 peptides. In cultured microglial cells, EP4 stimulation attenuated levels of A?42-induced inflammatory factors and potentiated phagocytosis of A?42. Microarray analysis was performed and demonstrated that EP4 stimulation broadly opposed A?42-driven gene expression changes in microglia, with enrichment for targets of IRF1, IRF7, and NF-?B transcription factors. Primary microglia were isolated from the brains of postnatal day 7 C57BL/6J mouse pups using the Neural Tissue Dissociation Kit (P), MACS Separation Columns (LS), and magnetic CD11b Microbeads from Miltenyi Biotec (Auburn, CA). Microglia from three separate litters of pups were maintained as three independent biological replicates for each treatment. After being cultured for three days, microglia were treated with oligomeric A?42 (10uM) and/or the specific EP4 agonist AE1-329 (100nM) for 6 hours. These 4 treatment conditions (A? + AE1, A? alone, AE1 alone, and vehicle alone) and 3 independent biological replicates per treatment gave us 12 total samples. After 6 hours of treatment, RNA was isolated from the microglia for microarray analysis.
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