Low levels of pro-resolving lipid mediators lipoxin-A4, resolvin-D1 and resolvin-E1 in patients with rheumatoid arthritis

Özdemir, Rabia Bilge Özgül; Gündüz, Özgül Soysal; Özdemir, Alper Tunga; Akgül, Özgür

doi:10.1016/j.imlet.2020.08.006

Cited by 30 publications

(10 citation statements)

References 32 publications

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“…As an anti-inflammatory and proresolving mediator, RvE1 is lower in the plasma of patients with chronic inflammation diseases than in healthy volunteers, which is negatively related to disease severity. 19,20,34 Accordingly, liquid chromatography-tandem mass spectrometry (Figure S1A in the Supplemental Material) revealed markedly reduced RvE1 levels in plasma from patients with idiopathic PAH as compared with plasma from healthy volunteers and in lung tissues from hypoxia-exposed mice and monocrotaline-treated rats as compared with tissues obtained from controls (Figure S1B through S1D). ChemR23, but not BLT1, was notably downregulated in both mouse and human PASMCs (Figure 1A) in response to hypoxia, as well as in pulmonary arteries (PAs) from experimental models of PH (Figure 1B and 1C).…”

Section: Resultsmentioning

confidence: 98%

Resolvin E1 Attenuates Pulmonary Hypertension by Suppressing Wnt7a/β-Catenin Signaling

et al. 2021

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Pulmonary arterial hypertension (PAH) is a devastating disease characterized by severe pulmonary vascular wall remodeling and perivascular inflammation. Resolvin E1 (RvE1), a proresolving lipid mediator, has protective effects against various inflammatory diseases. However, the effect of RvE1 on PAH development remains to be determined. We aimed to investigate whether RvE1 has a therapeutic effect on PAH and, if so, to elucidate the molecular mechanisms underlying its effects. A hypoxia+SU5416-induced mouse model of pulmonary hypertension (PH) and an monocrotaline-induced rat model of PH were used to test therapeutic effect of RvE1. Lung tissues and plasma samples were collected from patients with PAH and rodent models to examine RvE1 production and its receptor chemerin chemokine-like receptor 1 (ChemR23) expression. We observed that RvE1 generation was reduced in the plasma of patients with idiopathic PAH and in lungs from experimental rodent models of PH. ChemR23 expression was markedly downregulated in hypoxia-exposed mouse pulmonary artery smooth muscle cells (PASMCs) and pulmonary arteries from PH rodents and patients with idiopathic PAH. RvE1 treatment alleviated experimental PH in both male and female rodents by inhibiting PASMC proliferation. Deletion of ChemR23 in vascular SMCs abolished the protective effect of RvE1 against hypoxia+SU5416-induced PAH in mice. Mechanistically, the RvE1/ChemR23 axis suppressed hypoxia-induced PASMC proliferation by inhibiting proliferative wingless-type MMTV integration site family member 7a/β-catenin signaling. Activation of ChemR23 by RvE1 diminished wingless-type MMTV integration site family member 7a expression in PASMCs by inhibiting protein kinase A-mediated Egr2 (early growth response 2) phosphorylation at Ser349. Thus, the RvE1/ChemR23 axis represses experimental PAH by modulating wingless-type MMTV integration site family member 7a/β-catenin signaling in PASMCs and may serve as a therapeutic target for the management of PAH.

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Section: Resultsmentioning

confidence: 98%

Resolvin E1 Attenuates Pulmonary Hypertension by Suppressing Wnt7a/β-Catenin Signaling

et al. 2021

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“…Recent studies on the pathogenesis of inflammation showed that the persistence of chronic inflammation might be not only caused by the complicated and enormous inflammatory networks, but also the absence of resolution mechanism [40] . This resolution function is often fulfilled by some specific mediators in vivo such as resolving E1, lipoxin and annexin A1 [41] . They can facilitate the inflammation resolution, restore inflamed tissue and maintain the immune homeostasis.…”

Section: Resultsmentioning

confidence: 99%

Targeting the resolution pathway of inflammation using Ac2–26 peptide-loaded PEGylated lipid nanoparticles for the remission of rheumatoid arthritis

Qin

Fan

et al. 2021

Asian Journal of Pharmaceutical Sciences

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Rheumatoid arthritis (RA) is a common autoimmune disease characterized by joint inflammation and immune dysfunction. Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications, the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems. Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation. Ac2–26, a 25-amino acid peptide derived from Annexin A (a pro-resolving mediator), has shown good efficacy in the treatment of inflammatory disorders. However, the low bioavailability of Ac2–26 peptides hinders their efficacy in vivo . In this paper, we formed PEGylated lipid nanoparticles (LDNPs) by the co-assembly of l -ascorbyl palmitate (L-AP) and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn‑glycero-3-phosphoethanolamine (DSPE-PEG 2k ) to encapsulate and deliver Ac2–26 peptides to the arthritic rats. They showed good stability and biocompatibility. After being intravenously administrated, Ac2–26 peptide-loaded PEGylated lipid nanoparticles (ADNPs) showed the prolonged in vivo circulation time and enhanced accumulation in inflamed sites. In vivo therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology. Therefore, the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment.

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“…Resolvins might reduce inflammation through the stimulation of a number of signaling pathways (18). RvD1 plays a role in resolving acute inflammation, and a number display evidence for RvD1 mediating functions that are conserved in chronic inflammatory conditions, including RA, Sjogren's syndrome, Parkinson's disease and type 1 diabetes mellitus (19)(20)(21)(22). It should be noted that the lower plasma level of RvD1 is not universal in inflammation disease, where an exception has been reported in patients with inflammatory arthritis by Barden et al (23).…”

Section: Rvd1 Increased Treg Differentiation and Inhibited Th17 Differentiation By Upregulating Mir-30e-5pmentioning

confidence: 99%

Resolvin D1 Improves the Treg/Th17 Imbalance in Systemic Lupus Erythematosus Through miR-30e-5p

et al. 2021

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Resolvin D1 (RvD1) prompts inflammation resolution and regulates immune responses. We explored the effect of RvD1 on systemic lupus erythematosus (SLE) and investigated the correlation between RvD1 and Treg/Th17 imbalance, which is one of the major factors contributing to the pathogenesis of disease. SLE patients and healthy controls were recruited to determine plasma RvD1 levels. MRL/lpr lupus model was used to verify rescue of the disease phenotype along with Treg/Th17 ratio. Purified naive CD4+ T cells were used to study the effect of RvD1 on Treg/Th17 differentiation in vitro. Furthermore, small RNA Sequencing and transfection were performed successively to investigate downstream microRNAs. The result showed that the RvD1 level was significantly lower in active SLE patients compared with inactive status and controls. Moreover, The SLE disease activity index (SLEDAI) score had a significant negative correlation with RvD1 level. As expected, RvD1 treatment ameliorated disease phenotype and inflammatory response, improved the imbalanced Treg/Th17 in MRL/lpr mice. In addition, RvD1 increased Treg while reduced Th17 differentiation in vitro. Furthermore, miR-30e-5p was verified to modulate the Treg/Th17 differentiation from naïve CD4+ T cells as RvD1 downstream microRNA. In conclusion, RvD1 effectively ameliorates SLE progression through up-regulating Treg and down-regulating Th17 cells via miR-30e-5p.

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Low levels of pro-resolving lipid mediators lipoxin-A4, resolvin-D1 and resolvin-E1 in patients with rheumatoid arthritis

Cited by 30 publications

References 32 publications

Resolvin E1 Attenuates Pulmonary Hypertension by Suppressing Wnt7a/β-Catenin Signaling

Resolvin E1 Attenuates Pulmonary Hypertension by Suppressing Wnt7a/β-Catenin Signaling

Targeting the resolution pathway of inflammation using Ac2–26 peptide-loaded PEGylated lipid nanoparticles for the remission of rheumatoid arthritis

Resolvin D1 Improves the Treg/Th17 Imbalance in Systemic Lupus Erythematosus Through miR-30e-5p

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