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Rheumatoid Arthritis macrophages are primed for inflammation and display bioenergetic and functional alterations

ABSTRACT: Rheumatoid Arthritis macrophages are primed for inflammation and display bioenergetic and functional alterations

PROVIDER: PRJNA925817 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23148546.fastq.gz	Fastqsanger.gz
	SRR23148547.fastq.gz	Fastqsanger.gz
	SRR23148548.fastq.gz	Fastqsanger.gz
	SRR23148549.fastq.gz	Fastqsanger.gz
	SRR23148550.fastq.gz	Fastqsanger.gz

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Rheumatoid Arthritis macrophages are primed for inflammation and display bioenergetic and functional alterations

Project description:To investigate the pro-inflammatory and metabolic function of Rheumatoid Arthritis monocyte derived macrophages RNA sequencing was perfomed on polarised healthy and Rheumatoid Arthritis monocyte-derived macrophages

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Rheumatoid Arthritis circulating CD14+ monocytes are epigenetically primed [ChIP-seq]

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Rheumatoid arthritis macrophages are primed for inflammation and display bioenergetic and functional alterations.

Project description:ObjectivesMyeloid cells with a monocyte/macrophage phenotype are present in large numbers in the RA joint, significantly contributing to disease; however, distinct macrophage functions have yet to be elucidated. This study investigates the metabolic activity of infiltrating polarized macrophages and their impact on pro-inflammatory responses in RA.MethodsCD14+ monocytes from RA and healthy control (HC) bloods were isolated and examined ex vivo or following differentiation into 'M1/M2' macrophages. Inflammatory responses and metabolic analysis ± specific inhibitors were quantified by RT-PCR, western blot, Seahorse XFe technology, phagocytosis assays and transmission electron microscopy along with RNA-sequencing (RNA-seq) transcriptomic analysis.ResultsCirculating RA monocytes are hyper-inflammatory upon stimulation, with significantly higher expression of key cytokines compared with HC (P < 0.05) a phenotype which is maintained upon differentiation into mature ex vivo polarized macrophages. This induction in pro-inflammatory mechanisms is paralleled by cellular bioenergetic changes. RA macrophages are highly metabolic, with a robust boost in both oxidative phosphorylation and glycolysis in RA along with altered mitochondrial morphology compared with HC. RNA-seq analysis revealed divergent transcriptional variance between pro- and anti-inflammatory RA macrophages, revealing a role for STAT3 and NAMPT in driving macrophage activation states. STAT3 and NAMPT inhibition results in significant decrease in pro-inflammatory gene expression observed in RA macrophages. Interestingly, NAMPT inhibition specifically restores macrophage phagocytic function and results in reciprocal STAT3 inhibition, linking these two signalling pathways.ConclusionThis study demonstrates a unique inflammatory and metabolic phenotype of RA monocyte-derived macrophages and identifies a key role for NAMPT and STAT3 signalling in regulating this phenotype.

| S-EPMC10321118 | biostudies-literature

Rheumatoid arthritis

Project description:Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced inter-patient heterogeneity. To characterize RA at the molecular level and to uncover key pathomechanisms, we performed whole-genome gene expression analyses. Synovial tissues from rheumatoid arthritis patients were compared to those from osteoarthritis patients and to normal donors. Keywords: disease state analysis

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Rheumatoid Arthritis circulating CD14+ monocytes are epigenetically primed [ChIP-seq]

Project description:Peripheral blood samples were collected from healthy controls and rheumatoid arthritis patients (active disease: DAS28 > 2.7), subsequently CD14+ monocytes were isolated using a positive selection kit, ChIP-Seq was completed for H3K4me3 and H3K27me3.

2025-04-10 | GSE294235 | GEO

Proteomics analysis of Rheumatoid arthritis

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Differential DNA methylation in Rheumatoid arthritis

Project description:Genome-wide DNA methylation level was studied to determine whether Rheumatoid arthritis patients (cases) has methylation differences comparing to normal controls in PBLs. We used Illumina HumanMethylation450 BeadChip array to determine the genome-wide DNA methylation difference in PBLs from Rheumatoid arthritis patients (cases) and normal controls Bisulphite converted DNA from the Rheumatoid arthritis patients (cases) and normal controls were hybridized to the Illumina Illumina HumanMethylation450 BeadChip arrays

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Rheumatoid arthritis: aortic biopsies

Project description:Rheumatoid arthritis: aortic biopsies

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Rheumatoid arthritis: aortic biopsies

Project description:Analysis of biopsies of the ascending aorta from coronary artery disease patients with and without rheumatoid arthritis

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Differential DNA methylation in Rheumatoid arthritis

Project description:Genome-wide DNA methylation level was studied to determine whether Rheumatoid arthritis patients (cases) has methylation differences comparing to normal controls in peripheral blood leukocytes (PBLs). We used Illumina HumanMethylation450 BeadChip array to determine the genome-wide DNA methylation difference in PBLs from Rheumatoid arthritis patients (cases) and normal controls

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