Dataset Information

Rat plasma liquid chromatography MS/MS

ABSTRACT: LC-MS/MS performed in the plasma of rats subjected to macrophage administration into intervertebral disc herniated tissue (Mac6w group) and macrophage systemic depletion (CLP6w group), as well as in their respective control groups (L6w).

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Intervertebral Disc

SUBMITTER: Carla Cunha

LAB HEAD: Mário Barbosa

PROVIDER: PXD042802 | Pride | 2023-10-24

REPOSITORIES: Pride

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Publications

Macrophage-based therapy for intervertebral disc herniation: preclinical proof-of-concept.

Ribeiro-Machado Cláudia C Santos Susana G SG Amaral Inês A IA Caldeira Joana J Pereira Paulo P Barbosa Mário A MA Cunha Carla C

NPJ Regenerative medicine 20230710 1

Intervertebral disc (IVD) degeneration and herniation is a leading cause of disability globally and a large unmet clinical need. No efficient non-surgical therapy is available, and there is an urgency for minimally invasive therapies capable of restoring tissue function. IVD spontaneous hernia regression following conservative treatment is a clinically relevant phenomenon that has been linked to an inflammatory response. This study establishes the central role of macrophages in IVD spontaneous h ...[more]

PMID: 37429889

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Project description:Objectives: Pinolenic acid (PNLA), an omega-6 polyunsaturated fatty acid from pine nuts, has anti-inflammatory and anti-atherogenic effects. We aimed to investigate the direct anti-inflammatory effect and anti-atherogenic effects of PNLA on activated purified CD14 monocytes from peripheral blood of patients with rheumatoid arthritis (RA) in vitro. Methods: Flow cytometry was used to assess the proportions of CD14 monocytes expressing TNF-α, IL-6, IL-1β, and IL-8 in purified monocytes from patients with RA after lipopolysaccharide (LPS) stimulation with/without PNLA pre-treatment. The whole genomic transcriptome (WGT) profile of PNLA-treated, and LPS-activated monocytes from patients with active RA was investigated by RNA-sequencing. Results: PNLA reduced percentage of monocytes expressing cytokines: TNF-a by 23% (p=0.048), IL-6 by 25% (p=0.011), IL-1B by 23% (p=0.050), IL-8 by 20% (p=0.066). Pathway analysis identified upstream activation of peroxisomes proliferator-activated receptors (PPARs), sirtuin3, and let7miRNA, KLF15 which are anti-inflammatory and antioxidative. In contrast, DAP3, LIF and STAT3, which are involved in TNF-a, and IL-6 signal transduction, were inhibited. Canonical Pathway analysis showed that PNLA inhibited oxidative phosphorylation (p=9.14E-09) and mitochondrial dysfunction (p=4.18E-08), while the sirtuin (SIRTs) signalling pathway was activated (p=8.89E-06) which interfere with the pathophysiologic process of atherosclerosis. Many miRNAs were modulated by PNLA suggesting potential post-transcriptional regulation of metabolic and immune response that has not been described previously. Multiple miRNAs target pyruvate dehydrogenase kinase-4 (PDK4), single-immunoglobulin interleukin-1 receptor molecule (SIGIRR), mitochondrially encoded ATP synthase membrane subunit 6 (MT-ATP6) and Acetyl-CoA Acyltranferase2 (ACAA2); genes implicated in regulation of lipid and cell metabolism, inflammation, and mitochondrial dysfunction. Conclusion: PNLA has potential anti-atherogenic and immune-metabolic effects on monocytes that are pathogenic in RA and atherosclerosis. Dietary PNLA supplementation regulates key miRNAs that are involved in metabolic, mitochondrial, and inflammatory pathways.

			Action	DRS
	Combined_35samples.msf	Msf
	EXP1_L2w_1.raw	Raw
	EXP1_L2w_2.raw	Raw
	EXP1_L2w_3.raw	Raw
	EXP1_L2w_4.raw	Raw