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High salt reduces the activation of IL-4+IL-13 stimulated macrophages

ABSTRACT: High salt reduces the activation of IL-4+IL-13 stimulated macrophages

PROVIDER: PRJEB8115 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR713594.fastq.gz	Fastqsanger.gz
	ERR713595.fastq.gz	Fastqsanger.gz
	ERR713596.fastq.gz	Fastqsanger.gz
	ERR713597.fastq.gz	Fastqsanger.gz
	ERR713598.fastq.gz	Fastqsanger.gz

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High salt reduces the activation of IL-4+IL-13 stimulated macrophages

Project description:High salt reduces the activation of IL-4+IL-13 stimulated macrophages

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High salt reduces the activation of IL-4+IL-13 stimulated macrophages

Project description:High salt (NaCl) intake is a major risk factor for cardiovascular disease; high NaCl has also been shown to be a powerful modulator of pro-inflammatory immune cell polarization. To investigate the effect of high NaCl on the polarization of M(IL-4+IL-13) macrophages we performed gene expression analysis by microarray and genome wide histone modification (H3K4me3 and H4ac) analysis by ChIP-seq of murine bone marrow derived macrophages. Macrophages were polarized with recombinant IL-4 and IL-13 in vitro in the presence or absence of an additional 40mM of NaCl in the culture medium for 24h before analysis.

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High salt reduces the activation of IL-4+IL-13 stimulated macrophages

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Project description:This experiment aims to identify the biological pathways and diseases associated with the cytokine Interleukin 13 (IL-13) using gene expression measured in peripheral blood mononuclear cells (PBMCs). The experiment comprised of samples obtained from 3 healthy donors. The expression profiles of in vitro IL-13 stimulation were generated using RNA-seq technology for 3 PBMC samples at 24 hours. The transcriptional profiles of PBMCs without IL-13 stimulation were also generated to be used as controls. An IL-13R-alpha antagonist (Redpath et al. Biochemical Journal, 2013) was introduced into IL-13 stimulated PBMCs and the gene expression levels after 24h were profiled to examine the neutralization of IL-13 signaling by the antagonist.

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High salt reduces the activation of IL-4- and IL-13-stimulated macrophages.

Project description:A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis.

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