MCTR3 reprograms arthritic monocytes to upregulate Arginase-1 and exert pro-resolving and tissue-protective functions in experimental arthritis

Pistorius, Kimberly; Ly, Lucy; Souza, Patricia R.; Gómez, Esteban A.; Koenis, Duco S.; Rodrı́guez, Ana R.; Foster, Julie; Sosabowski, Jane; Hopkinson, Mark; Rajeeve, Vinothini; Spur, B.; Pitsillides, Andrew A.; Pitzalis, Costantino; Dalli, Jesmond

doi:10.1016/j.ebiom.2022.103974

Cited by 8 publications

(5 citation statements)

References 74 publications

(117 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MCTR3 potently decreased joint inflammation and promoted tissue repair. MCTR3 was mediated via the reprogramming of circulating monocytes to yield macrophages, upregulating arginase-1 to enhance the pro-resolving inflammation and tissue repair function [ 135 ].…”

Section: Resultsmentioning

confidence: 99%

Maresin: Macrophage Mediator for Resolving Inflammation and Bridging Tissue Regeneration—A System-Based Preclinical Systematic Review

Liu

Yang

Wang

et al. 2023

IJMS

View full text Add to dashboard Cite

Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and potentially serving as a therapeutic agent for chronic inflammatory diseases. The aim of this review was to systematically investigate preclinical and clinical studies on maresin to inform translational research. Two independent reviewers performed comprehensive searches with the term “Maresin (NOT) Review” on PubMed. A total of 137 studies were included and categorized into 11 human organ systems. Data pertinent to clinical translation were specifically extracted, including delivery methods, optimal dose response, and specific functional efficacy. Maresins generally exhibit efficacy in treating inflammatory diseases, attenuating inflammation, protecting organs, and promoting tissue regeneration, mostly in rodent preclinical models. The nervous system has the highest number of original studies (n = 25), followed by the cardiovascular system, digestive system, and respiratory system, each having the second highest number of studies (n = 18) in the field. Most studies considered systemic delivery with an optimal dose response for mouse animal models ranging from 4 to 25 μg/kg or 2 to 200 ng via intraperitoneal or intravenous injection respectively, whereas human in vitro studies ranged between 1 and 10 nM. Although there has been no human interventional clinical trial yet, the levels of MaR1 in human tissue fluid can potentially serve as biomarkers, including salivary samples for predicting the occurrence of cardiovascular diseases and periodontal diseases; plasma and synovial fluid levels of MaR1 can be associated with treatment response and defining pathotypes of rheumatoid arthritis. Maresins exhibit great potency in resolving disease inflammation and bridging tissue regeneration in preclinical models, and future translational development is warranted.

show abstract

Section: Resultsmentioning

confidence: 99%

Maresin: Macrophage Mediator for Resolving Inflammation and Bridging Tissue Regeneration—A System-Based Preclinical Systematic Review

Liu

Yang

Wang

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…To that end, we measured global protein phosphorylation changes in human macrophages treated with MCTR1, MCTR2, or MCTR3 using label‐free mass spectrometry as previously described. [ 24 ] We then analyzed the data using Partial Least Squares Discriminant analysis (PLS‐DA), a type of multivariate analysis that reduces dataset dimensions and identifies the relationship between samples based on differences in phosphopeptide abundance. This analysis showed a clear separation between Vehicle control versus MCTR‐treated macrophage groups with a coefficient‐of‐determination ( R 2 ) of 0.89 (Figure S5A, Supporting Information), indicating a strong ability of the model to explain the differences between these four groups.…”

Section: Resultsmentioning

confidence: 99%

“…After trypsin digestion, phosphopeptides were enriched from total peptides by TiO 2 chromatography as previously described. [ 24 ] Dried phosphopeptides were dissolved in 0.1% trifluoroacetic acid and analyzed using an UltiMate 3000 RSLCnano coupled on‐line to a Q‐Exactive Plus mass spectrometer (Thermo Fisher Scientific). Elution was performed using a gradient of 3% to 35% buffer B (0.1% formic acid in acetonitrile) over 120 min at a flow rate of 300 nL min −1 with buffer A (0.1% formic acid in water) being used to balance the mobile phase.…”

Section: Methodsmentioning

confidence: 99%

Efferocyte‐Derived MCTRs Metabolically Prime Macrophages for Continual Efferocytosis via Rac1‐Mediated Activation of Glycolysis

Koenis,

de Matteis,

Rajeeve

et al. 2023

Advanced Science

Self Cite

View full text Add to dashboard Cite

Clearance of multiple rounds of apoptotic cells (ACs) through continual efferocytosis is critical in the maintenance of organ function, the resolution of acute inflammation, and tissue repair. To date, little is known about the nature of mechanisms and factors that govern this fundamental process. Herein, the authors reported that breakdown of ACs leads to upregulation of 12‐lipoxygenase in macrophages. This enzyme converts docosahexaenoic acid to maresin conjugates in tissue regeneration (MCTRs). The levels of these autacoids are elevated at sites of high apoptotic burden in vivo and in efferocytosing macrophages in vitro. Abrogation of MCTR production using genetic approaches limits the ability of macrophages to perform continual efferocytosis both in vivo and in vitro, an effect that is rescued by add‐back of MCTRs. Mechanistically, MCTR‐mediated priming of macrophages for continual efferocytosis is dependent on alterations in Rac1 signalling and glycolytic metabolism. Inhibition of Rac1 abolishes the ability of MCTRs to increase glucose uptake and efferocytosis in vitro, whereas inhibition of glycolysis limits the MCTR‐mediated increases in efferocytosis and tissue repair. Together, these findings demonstrate that upregulation of MCTRs by efferocytosing macrophages plays a central role in the regulation of continual efferocytosis via the autocrine and paracrine modulation of metabolic pathways.

show abstract

“…Each LM was identified using established criteria, including 1) matching retention time to synthetic and authentic materials, 2) the integrated peak consists of at least 7 data points, and 3) the signal-to-noise ratio of the integrated peak is at least 5. Calibration curves were obtained for each using synthetic compound mixtures at 0.78, 1.56, 3.12, 6.25, 12.5, 25, 50, 100, and 200 pg that gave linear calibration curves with an r 2 values of 0.98–0.99 [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice

Laiglesia

Escoté

Sáinz

et al. 2023

Molecular Metabolism

Self Cite

View full text Add to dashboard Cite

MCTR3 reprograms arthritic monocytes to upregulate Arginase-1 and exert pro-resolving and tissue-protective functions in experimental arthritis

Cited by 8 publications

References 74 publications

Maresin: Macrophage Mediator for Resolving Inflammation and Bridging Tissue Regeneration—A System-Based Preclinical Systematic Review

Maresin: Macrophage Mediator for Resolving Inflammation and Bridging Tissue Regeneration—A System-Based Preclinical Systematic Review

Efferocyte‐Derived MCTRs Metabolically Prime Macrophages for Continual Efferocytosis via Rac1‐Mediated Activation of Glycolysis

Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice

Contact Info

Product

Resources

About