Maresin 1 activates LGR6 receptor promoting phagocyte immunoresolvent functions

Chiang, Nan; Libreros, Stephania; Norris, Paul C.; Rosa, Xavier de la; Serhan, Charles N.

doi:10.1172/jci129448

Cited by 178 publications

(170 citation statements)

References 50 publications

(94 reference statements)

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“…In this study, we measured the expression of ChemR23 and confirmed the presence of ChemR23 expression on the hPDLSCs (data not shown). Very recently, the LGR6 has been identified as the receptor for MaR1 for the first time on phagocytes (76). In line with this work and other recent studies on pre-osteoblasts (77) and BMSCs (78), our ongoing studies are focusing on the impact of inflammation on the expression of these receptors and their downstream signaling in hPDLSCs.…”

Section: Discussionsupporting

confidence: 53%

Maresin-1 and Resolvin E1 Promote Regenerative Properties of Periodontal Ligament Stem Cells Under Inflammatory Conditions

Albuquerque‐Souza

Schulte

Chen³

et al. 2020

Front. Immunol.

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Maresin-1 (MaR1) and Resolvin E1 (RvE1) are specialized pro-resolving lipid mediators (SPMs) that regulate inflammatory processes. We have previously demonstrated the hard and soft tissue regenerative capacity of RvE1 in an in vivo model of the periodontal disease characterized by inflammatory tissue destruction. Regeneration of periodontal tissues requires a well-orchestrated process mediated by periodontal ligament stem cells. However, limited data are available on how SPMs can regulate the regenerative properties of human periodontal ligament stem cells (hPDLSCs) under inflammatory conditions. Thus, we measured the impact of MaR1 and RvE1 in an in vitro model of hPDLSC under stimulation with IL-1β and TNF-α by evaluating pluripotency, migration, viability/cell death, periodontal ligament markers (α-smooth muscle actin, tenomodulin, and periostin), cementogenic-osteogenic differentiation, and phosphoproteomic perturbations. The data showed that the pro-inflammatory milieu suppresses pluripotency, viability, and migration of hPDLSCs; MaR1 and RvE1 both restored regenerative capacity by increasing hPDLSC viability, accelerating wound healing/migration, and up-regulating periodontal ligament markers and cementogenicosteogenic differentiation. Protein phosphorylation perturbations were associated with the SPM-induced regenerative capacity of hPDLSCs. Together, these results demonstrate that MaR1 and RvE1 restore or improve the regenerative properties of highly specialized stem cells when inflammation is present and offer opportunities for direct pharmacologic treatment of lost tissue integrity.

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Section: Discussionsupporting

confidence: 53%

Maresin-1 and Resolvin E1 Promote Regenerative Properties of Periodontal Ligament Stem Cells Under Inflammatory Conditions

Albuquerque‐Souza

Schulte

Chen³

et al. 2020

Front. Immunol.

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“…This possibility could be partly supported by the specialized proresolving mediators of DHA and EPA derivatives, such as resolvin D1, resolvin D2, resolvin E, protectin D1, and maresin 1 [ 34 ]. Their corresponding G protein-coupled receptors (GPCRs), such as GPR32, GPR18, ChemR23, GPR37, and LGR6, have been found to function as anti-inflammatory and proresolving receptors [ 34 – 40 ]. Therefore, the beneficial effects of omega-3 polyunsaturated fatty acids may partially result from the direct activation of FFA4 and partially from the indirect activation of the GPCRs of specialized proresolving mediators [ 34 – 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…Their corresponding G protein-coupled receptors (GPCRs), such as GPR32, GPR18, ChemR23, GPR37, and LGR6, have been found to function as anti-inflammatory and proresolving receptors [ 34 – 40 ]. Therefore, the beneficial effects of omega-3 polyunsaturated fatty acids may partially result from the direct activation of FFA4 and partially from the indirect activation of the GPCRs of specialized proresolving mediators [ 34 – 40 ]. Because compound A still has a low affinity for FFA4, we used a high dose of compound A (30 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

Free fatty acid receptor 4 (FFA4) activation ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by increasing regulatory T cells in mice

et al. 2020

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High dose intake of docosahexaenoic acid showed beneficial effects on atopic dermatitis in patients and was found to increase regulatory T cells in mice, but its molecular target has not been identified. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor sensing polyunsaturated long-chain fatty acids including docosahexaenoic acid. In the present study, we examined whether FFA4 acted as a therapeutic target of docosahexaenoic acid for treating atopic dermatitis. Experimental atopic dermatitis was induced in mice by 2,4-dinitrochlorobenzene (DNCB) sensitization on day 0, followed by repeated DNCB challenges from D7 to D48. The mice were treated with a selective agonist compound A (30 mg· kg −1 · d −1 , ip) from D19 to D48, and sacrificed on D49. We found that DNCB-induced atopic dermatitis-like skin lesions, i.e. hypertrophy and mast cell infiltration in skin tissues, as well as markedly elevated serum IgE levels. Administration of compound A significantly suppressed the atopic responses in ears and lymph nodes, such as hypertrophy and mast cell infiltration in the ears, enlarged sizes of lymph nodes, and elevated serum IgE and levels of cytokines IL-4, IL-13, IL-17, and IFN-γ in ear tissue. The therapeutic effects of compound A were abolished by FFA4 knockout. Similarly, increased CD4 + Foxp3 + regulatory T-cell population in lymph nodes was observed in wide-type mice treated with compound A, but not seen in FFA4-deficient mice. In conclusion, we demonstrate that activation of FFA4 ameliorates atopic dermatitis by increasing CD4 + Foxp3 + regulatory T cells, suggesting FFA4 as a therapeutic target for atopic dermatitis.

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“…RvE1 binds to chemerin receptor 23 (ChemR23) and the leukotriene B4 receptor 1 (BLT1) [72]. Leucine-rich repeat containing G protein-coupled receptor 6 (LGR6) and G protein-coupled receptor (GPR37) are thought to be possible receptors for MaR1 and NPD1, respectively [73][74][75][76][77] (Figure 1). Since pro-inflammatory ligands aside from SPMs also bind to these receptors [71,78,79], very low concentrations of SPMs can bind to their receptors and signal the resolution of inflammation [77].…”

Section: Spms (Specialized Pro-resolving Lipid Mediators)mentioning

confidence: 99%

Alzheimer’s Disease and Specialized Pro-Resolving Lipid Mediators: Do MaR1, RvD1, and NPD1 Show Promise for Prevention and Treatment?

Miyazawa

Fukunaga

Tatewaki

et al. 2020

IJMS

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Alzheimer’s disease (AD) is a common neurodegenerative disease and a major contributor to progressive cognitive impairment in an aging society. As the pathophysiology of AD involves chronic neuroinflammation, the resolution of inflammation and the group of lipid mediators that actively regulate it—i.e., specialized pro-resolving lipid mediators (SPMs)—attracted attention in recent years as therapeutic targets. This review focuses on the following three specific SPMs and summarizes their relationships to AD, as they were shown to effectively address and reduce the risk of AD-related neuroinflammation: maresin 1 (MaR1), resolvin D1 (RvD1), and neuroprotectin D1 (NPD1). These three SPMs are metabolites of docosahexaenoic acid (DHA), which is contained in fish oils and is thus easily available to the public. They are expected to become incorporated into promising avenues for preventing and treating AD in the future.

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Maresin 1 activates LGR6 receptor promoting phagocyte immunoresolvent functions

Cited by 178 publications

References 50 publications

Maresin-1 and Resolvin E1 Promote Regenerative Properties of Periodontal Ligament Stem Cells Under Inflammatory Conditions

Maresin-1 and Resolvin E1 Promote Regenerative Properties of Periodontal Ligament Stem Cells Under Inflammatory Conditions

Free fatty acid receptor 4 (FFA4) activation ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by increasing regulatory T cells in mice

Alzheimer’s Disease and Specialized Pro-Resolving Lipid Mediators: Do MaR1, RvD1, and NPD1 Show Promise for Prevention and Treatment?

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