Imbalanced serum levels of resolvin E1 (RvE1) and leukotriene B4 (LTB4) in patients with allergic rhinitis

Lotfi, Ramin; Davoodi, Akram; Mortazavi, Seyed Hamidreza; Karaji, Ali Gorgin; Tarokhian, Hanieh; Rezaiemanesh, Alireza; Salari, Farhad

doi:10.1007/s11033-020-05849-x

Cited by 11 publications

(11 citation statements)

References 60 publications

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“…We confirmed previous reports that RvE1 is a BLT 1 agonist, with potencies in the mid-high nanomolar range across different assays. However, previous studies identified RvE1 in serum at low picomolar concentrations (Lotfi et al, 2020), perhaps questioning the physiological role of this ligand at BLT 1 . We also verified robust chemerin activity at chemerin 1 in both cAMP inhibition and ERK1/2 phosphorylation assays.…”

Section: Discussionmentioning

confidence: 86%

Multipathway In Vitro Pharmacological Characterization of Specialized Proresolving G Protein-Coupled Receptors

et al. 2022

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Specialised pro-resolving mediators (SPMs) and their cognate G protein-coupled receptors are implicated in autoimmune disorders including chronic inflammation, rheumatoid arthritis, systemic scleroderma, and lupus erythematosus. To date six GPCRs have been paired with numerous endogenous and synthetic ligands. However, the function and downstream signalling of these receptors remains unclear. To address this knowledge gap, we systematically expressed each receptor in a HEK293-Flp-In-CD8a-FLAG cell system. Each receptor was pharmacologically characterised with both synthetic and putative endogenous ligands across different signalling assays, covering both G protein-dependent (G s , G i and G q ), and independent mechanisms (β-arrestin2 recruitment). Three orphan GPCRs previously identified as SPM receptors (GPR18, GPR32 and GPR37) failed to express in HEK293 cells. While we were unsuccessful in identifying an endogenous ligand for FPR2/ALX, with only a modest response to fMLP, we did reveal clear signalling bias away from ERK1/2 phosphorylation for the clinically tested agonist ACT-389949, adding further evidence for its poor efficacy in two phase I studies. We also identified neuroprotectin D1 as a new BLT 1 agonist, implying an alternative target for the neuroprotective effects of the ligand. We confirmed activity for RvE1 at BLT 1 but failed to observe any response at the chemerin 1 receptor. This study provides some much-needed clarity around published receptor-ligand pairings but indicates that the expression and function of these SPM GPCRs remains very much context-dependent. In addition, the identification of signalling bias at FPR2/ALX may assist in guiding design of new FPR2/ALX agonists for the treatment of autoimmune disorders.

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Section: Discussionmentioning

confidence: 86%

Multipathway In Vitro Pharmacological Characterization of Specialized Proresolving G Protein-Coupled Receptors

et al. 2022

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“…[14] When exposed to allergens, IgE acts on mast cells, which in turn release a series of cytokines such as histamine, tumor necrosis factor-α (TNF-α), and leukotriene, resulting in further aggravation of AR. [15] The THD mentioned in this study has been shown to be effective in controlling the symptoms of AR and reducing the number of AR attacks in patients. The theoretical concepts of network pharmacology are coincide with the multi-components and multi-targets of TCM, it can serve as a significant method to analyze drugs, components, and diseases targets.…”

Section: Discussionmentioning

confidence: 97%

Investigating the mechanism of Tongqiao Huoxue decotion in the treatment of allergic rhinitis based on network pharmacology and molecular docking: A review

Zhang

et al. 2023

Medicine

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Allergic rhinitis is prone to recurrence, and clinical treatments focus on control symptoms; however there is no radical cure. Our aim was to use network pharmacology and molecular docking to reveal the hub genes, biological functions, and signaling pathways of Tongqiao Huoxue decoction against allergic rhinitis. First, the chemical components and target genes of Tongqiao Huoxue decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology database. Similarly, allergic rhinitis targets were screened using online Mendelian Inheritance In Man and GeneCards database. Then, all potential targets of Tongqiao Huoxue decoction in the treatment of allergic rhinitis were identified, the Venn diagram was portrayed using R software, and protein-protein interaction network was built using String. The hub genes were analyzed using enrichment analyses. Finally, molecular docking was used to verify the reliability of the key gene prediction. The core targets for Tongqiao Huoxue decoction to improve allergic rhinitis were AKT1, TP53, IL6, and so on. The enrichment analysis results showed that Tongqiao Huoxue decoction treatment in allergic rhinitis might be involved in the AGE-RAGE signaling pathway and fluid shear stress and atherosclerosis pathway. The molecular docking verification indicated that its ingredients bound well to the core targets of allergic rhinitis, and stigmasterol's docking ability with TNF (−12.73 kcal/mol) is particularly prominent. Based on these findings, it may be deduced that stigmasterol treated allergic rhinitis by acting on TNF targets. But, this conclusion needs to be confirmed by further in vitro and in vivo trials.

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“…In physiological conditions, mature neutrophils are governed by circadian oscillations within the hematopoietic niche that is orchestrated by the microbiome and clock-related genes, notably Bmal1 and CXCR2 [132,133]. Specifically, Bmal1 and CXCL2 regulate circadian oscillation of neutrophil gene expression and granule content [1,128]. Bone marrow neutrophil maturation and mobilization into the peripheral blood is controlled by CXCR2 and CXCR4 [134,135].…”

Section: Resolvins: New Players In Bone Marrow Dynamicsmentioning

confidence: 99%

“…Excessive levels of LTB 4 are shown in chronic inflammatory diseases like arthritis, cancer, metabolic disorders, and cardiovascular diseases [127]. It has been proposed the ratio between LTB 4 levels and SPMs in serum may predict disease outcome; for instance, a high ratio is associated with delayed inflammation resolution and atherosclerosis progression [37,73], airway inflammation [128], and ischemic stroke [53]. BLT1 knockout mice show reduced plaque formation, implicating LTB 4 in disease progression.…”

Section: Leukotriene B4 and Specialized Pro-resolving Mediators Are C...mentioning

confidence: 99%

Lipid mediators in neutrophil biology: inflammation, resolution and beyond

Ghodsi,

Hidalgo,

Libreros

2024

Current Opinion in Hematology

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Purpose of review Acute inflammation is the body's first defense in response to pathogens or injury. Failure to efficiently resolve the inflammatory insult can severely affect tissue homeostasis, leading to chronic inflammation. Neutrophils play a pivotal role in eradicating infectious pathogens, orchestrating the initiation and resolution of acute inflammation, and maintaining physiological functions. The resolution of inflammation is a highly orchestrated biochemical process, partially modulated by a novel class of endogenous lipid mediators known as specialized pro-resolving mediators (SPMs). SPMs mediate their potent bioactions via activating specific cell-surface G protein-coupled receptors (GPCR). Recent findings This review focuses on recent advances in understanding the multifaceted functions of SPMs, detailing their roles in expediting neutrophil apoptosis, promoting clearance by macrophages, regulating their excessive infiltration at inflammation sites, orchestrating bone marrow deployment, also enhances neutrophil phagocytosis and tissue repair mechanisms under both physiological and pathological conditions. We also focus on the novel role of SPMs in regulating bone marrow neutrophil functions, differentiation, and highlight open questions about SPMs’ functions in neutrophil heterogeneity. Summary SPMs play a pivotal role in mitigating excessive neutrophil infiltration and hyperactivity within pathological milieus, notably in conditions such as sepsis, cardiovascular disease, ischemic events, and cancer. This significant function highlights SPMs as promising therapeutic agents in the management of both acute and chronic inflammatory disorders.

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Imbalanced serum levels of resolvin E1 (RvE1) and leukotriene B4 (LTB4) in patients with allergic rhinitis

Cited by 11 publications

References 60 publications

Multipathway In Vitro Pharmacological Characterization of Specialized Proresolving G Protein-Coupled Receptors

Multipathway In Vitro Pharmacological Characterization of Specialized Proresolving G Protein-Coupled Receptors

Investigating the mechanism of Tongqiao Huoxue decotion in the treatment of allergic rhinitis based on network pharmacology and molecular docking: A review

Lipid mediators in neutrophil biology: inflammation, resolution and beyond

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