Ligands and Signaling of Mas-Related G Protein-Coupled Receptor-X2 in Mast Cell Activation

Mi, Yan-ni; Ping, Nana; Cao, Ricardo

doi:10.1007/112_2020_53

Cited by 14 publications

(8 citation statements)

References 187 publications

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“…Mast cell degranulation can be induced by a rapid and transient Ca 2+ mobilization, which is triggered by calcium signal pathway (Ali, 2017). Both MAPK and NF‐κB pathways are involved in the MRGPRX2‐induced inflammatory mediators release (Mi et al, 2021). PI3K/Akt is also involved in MRGPRX2‐mediated calcium flux (Zhang et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Silibinin attenuated pseudo‐allergic reactions and mast cell degranulation via PLCγ and PI3K/Akt signaling pathway

Wang

Dang

et al. 2023

Phytotherapy Research

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Anaphylaxis is a type of potentially fatal hypersensitivity reaction resulting from the activation of mast cells. Many endogenous or exogenous factors could cause this reaction. Silibinin is the main chemical component of silymarin and has been reported to have pharmacological activities. However, the anti‐allergic reaction effect of silibinin has not yet been investigated. This study aimed to evaluate the effect of silibinin to attenuate pseudo‐allergic reactions in vivo and to investigate the underlying mechanism in vitro. In this study, calcium imaging was used to assess Ca2+ mobilization. The levels of cytokines and chemokines, released by stimulated mast cells, were measured using enzyme immunoassay kits. The activity of silibinin was evaluated in a mouse model of passive cutaneous anaphylaxis (PCA). Western blotting was used to explore the related molecular signaling pathways. In results, silibinin markedly inhibited mast cell degranulation, calcium mobilization, and preventing the release of cytokines and chemokines in a dose‐dependent manner via the PLCγ and PI3K/Akt signaling pathway. Silibinin also attenuated PCA in a dose‐dependent manner. In summary, silibinin has an anti‐pseudo‐allergic pharmacological activity, which makes it a potential candidate for the development of a novel agent to arrest pseudo‐allergic reactions.

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Section: Discussionmentioning

confidence: 99%

Silibinin attenuated pseudo‐allergic reactions and mast cell degranulation via PLCγ and PI3K/Akt signaling pathway

Wang

Dang

et al. 2023

Phytotherapy Research

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“…Recent studies reported the agonist-stabilized structures of MrgX2 and found that the extracellular region of MrgX2 was indeed the ligand binding surface and the intracellular domain was related to G protein coupling and downstream signal transduction [27,28]. As MrgX2 was fused with SNAP-tag at its C-terminus, then immobilized onto matrix in an orderly manner, leading to exposure of its extracellular domain for ligand screening.…”

Section: Discussionmentioning

confidence: 99%

MrgX2-SNAP-tag/cell membrane chromatography model coupled with liquid chromatography-mass spectrometry for anti-pseudo-allergic compound screening in Arnebiae Radix

Jia

Gao

et al. 2022

Anal Bioanal Chem

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Pseudo-allergic reactions (PARs) are IgE-independent hypersensitivity reactions. Mas-related G protein-coupled receptor-X2 (MrgX2) was proved the key receptor of PAR. The anti-pseudo-allergic compound discovery based on MrgX2 was of great value. Cell membrane chromatography (CMC) based on MrgX2 provides a convenient and effective tool in anti-pseudoallergic compound screening and discovery, and further improvements of this method are still needed. In this work, SNAPtag was introduced at C-terminal of Mas-related G protein-coupled receptor (MrgX2-SNAP-tag), and an MrgX2-SNAP-tag/ CMC model was then conducted using CMC technique. Comparative experiments showed that the new model not only satisfied the good selectivity and specificity of screening but also exhibited more stable and longer life span than traditional MrgX2/CMC model. By coupling with HPLC-MS, two compounds were screened out from Arnebiae Radix and identified as shikonin and acetylshikonin. Nonlinear chromatography was performed to study the interactions between two screened compounds and MrgX2, and binding constant (K A ) of shikonin and acetylshikonin with MrgX2 were 2075.67 ± 0.34 M −1 and 32201.36 ± 0.35 M −1 , respectively. Furthermore, β-hexosaminidase and histamine release assay in vitro demonstrated that shikonin (1-5 μM) and acetylshikonin (2.5-10 μM) could both antagonize C48/80-induced allergic reaction. In conclusion, the MrgX2-SNAP-tag/CMC could be a reliable model for screening pseudo-allergy-related components from complex systems.

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“…PAF is capable of activating MCs and inducing a chemotactic response. COVID-19 manifestations, including pulmonary microthrombosis and inflammation, are mediated via PAF receptor [ 140 ] MRGPRX2 is a novel, low-affinity and low-selectivity receptor, to activate MCs in an IgE-independent manner [ 141 ]. This receptor has been cited as a therapeutic target for COVID-19 [ 142 ] MCs respond to TLR ligands by secreting cytokines, chemokines, and lipid mediators, and some studies have found that TLR ligands can also cause degranulation, although this finding is contentious [ 143 ] Several clinical investigations revealed that chemokines are directly involved in the different stages of SARS-CoV-2 infection [ 144 ].…”

Section: Secretory Activity Of Mcs: Main Categories Of the Mediators ...mentioning

confidence: 99%

“…MRGPRX2 is a novel, low-affinity and low-selectivity receptor, to activate MCs in an IgE-independent manner [ 141 ]. This receptor has been cited as a therapeutic target for COVID-19 [ 142 ]…”

Section: Secretory Activity Of Mcs: Main Categories Of the Mediators ...mentioning

confidence: 99%

Mast Cell Activation Syndrome in COVID-19 and Female Reproductive Function: Theoretical Background vs. Accumulating Clinical Evidence

Szukiewicz

Wątroba

Szewczyk

2022

Journal of Immunology Research

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Coronavirus disease 2019 (COVID-19), a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, can affect almost all systems and organs of the human body, including those responsible for reproductive function in women. The multisystem inflammatory response in COVID-19 shows many analogies with mast cell activation syndrome (MCAS), and MCAS may be an important component in the course of COVID-19. Of note, the female sex hormones estradiol (E2) and progesterone (P4) significantly influence mast cell (MC) behavior. This review presents the importance of MCs and the mediators from their granules in the female reproductive system, including pregnancy, and discusses the mechanism of potential disorders related to MCAS. Then, the available data on COVID-19 in the context of hormonal disorders, the course of endometriosis, female fertility, and the course of pregnancy were compiled to verify intuitively predicted threats. Surprisingly, although COVID-19 hyperinflammation and post-COVID-19 illness may be rooted in MCAS, the available clinical data do not provide grounds for treating this mechanism as significantly increasing the risk of abnormal female reproductive function, including pregnancy. Further studies in the context of post COVID-19 condition (long COVID), where inflammation and a procoagulative state resemble many aspects of MCAS, are needed.

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Ligands and Signaling of Mas-Related G Protein-Coupled Receptor-X2 in Mast Cell Activation

Cited by 14 publications

References 187 publications

Silibinin attenuated pseudo‐allergic reactions and mast cell degranulation via PLCγ and PI3K/Akt signaling pathway

Silibinin attenuated pseudo‐allergic reactions and mast cell degranulation via PLCγ and PI3K/Akt signaling pathway

MrgX2-SNAP-tag/cell membrane chromatography model coupled with liquid chromatography-mass spectrometry for anti-pseudo-allergic compound screening in Arnebiae Radix

Mast Cell Activation Syndrome in COVID-19 and Female Reproductive Function: Theoretical Background vs. Accumulating Clinical Evidence

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