Potential Role of Moesin in Regulating Mast Cell Secretion

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(15), С. 12081 - 12081

Опубликована: Июль 28, 2023

Mast cells have existed for millions of years in species that never suffer from allergic reactions. Hence, addition to allergies, mast can play a critical role homeostasis and inflammation via secretion numerous vasoactive, pro-inflammatory neuro-sensitizing mediators. Secretion may utilize different modes involve the cytoskeleton, but our understanding molecular mechanisms regulating is still not well understood. The Ezrin/Radixin/Moesin (ERM) family proteins involved linking cell surface-initiated signaling actin cytoskeleton. However, how ERMs regulate poorly contain two functional domains connected through long α-helix region, N-terminal FERM (band 4.1 protein-ERM) domain C-terminal ERM association (C-ERMAD). C-ERMAD bind each other head-to-tail manner, leading closed/inactive conformation. Typically, phosphorylation on C-terminus Thr has been associated with activation ERMs, including macrophages platelets. It previously shown ability so-called “stabilizer” disodium cromoglycate (cromolyn) inhibit rat closely paralleled 78 kDa protein, which was subsequently be moesin, member ERMs. Interestingly, moesin during inhibition Ser56/74 Thr66 residues. This pattern could lock its inactive state render it inaccessible binding Soluble NSF attachment protein receptors (SNAREs) synaptosomal-associated (SNAPs) exocytosis. Using confocal microscopic imaging, we showed found colocalize cluster around secretory granules secretion. In conclusion, localization important regulation targeted development effective inhibitors inflammatory mediators cells.

Язык: Английский

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The regulatory role and mechanism of mast cells in tumor microenvironment

American Journal of Cancer Research, Год журнала: 2024, Номер 14(1), С. 1 - 15

Опубликована: Янв. 1, 2024

Mast cells (MCs) have emerged as pivotal contributors to both the defensive immune response and immunomodulation. They also exhibit regulatory functions in modulating pathological processes across various allergic diseases. The impact of MC presence within tumor tissues has garnered considerable attention, yielding conflicting findings. While some studies propose that MCs promote initiation progression, others advocate an opposing perspective. Notably, evidence emphasizes dual role cancer, promoters suppressors, is crucial for optimizing cancer treatment strategies. These viewpoints generated substantial controversy, underscoring need a comprehensive understanding MC's responses.

Язык: Английский

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Licochalcone A inhibits MAS‐related GPR family member X2‐induced pseudo‐allergic reaction by suppressing nuclear migration of nuclear factor‐κB

Phytotherapy Research, Год журнала: 2021, Номер 35(11), С. 6270 - 6280

Опубликована: Сен. 5, 2021

Licochalcone A (Lico A) is a natural flavonoid belonging to the class of substituted chalcone that has various biological effects. Mast cells (MCs) are innate immune mediate hypersensitivity and pseudo-allergic reactions. MAS-related GPR family member X2 (MRGPRX2) on MCs been recognized as main receptor for In this study, we investigated anti-pseudo-allergy effect Lico its underlying mechanism. Substance P (SP), an MC activator, was used establish in vitro vivo model pseudo-allergy. The using passive cutaneous anaphylaxis (PCA) active systemic allergy, along with degranulation, Ca2+ influx vitro. SP-induced laboratory allergic disease 2 (LAD2) cell mRNA expression explored RNA-seq, inhibited LAD2 activation by reverse transcription polymerase chain reaction (RT-PCR), western blotting, immunofluorescence staining. showed inhibitory pseudo-allergy both vivo. nuclear factor (NF)-κB pathway involved MRGPRX2 induced activation, which A. conclusion, mediated blocking NF-κB migration.

Язык: Английский

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Degranulation of human mast cells: modulation by P2 receptors’ agonists

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Окт. 5, 2023

Since the late 1970s, there has been an alarming increase in incidence of asthma and its morbidity mortality. Acute obstruction inflammation allergic asthmatic airways are frequently caused by inhalation exogenous substances such as allergens cross-linking IgE receptors expressed on surface human lung mast cells (HLMC). The degree constriction produced identical amounts inhaled may vary from day to even hour hour. Endogenous factors cell (HMC)’s microenvironment during allergen exposure markedly modulate degranulation response. An responsiveness significantly enhance bronchoconstriction breathlessness. This review focuses role that ubiquitous endogenous purine nucleotide, extracellular adenosine 5’-triphosphate (ATP), which is a component damage-associated molecular patterns, plays cells’ physiology. ATP activates P2 purinergic cell-surface (P2R) trigger signaling cascades resulting heightened inflammatory responses. most potent enhancer IgE-mediated HLMC described date. Current knowledge it relates targeted receptor(s) HMC along with recent studies exploring post-receptor activation pathways discussed. In addition, reviewed explain why brief, minimal exposures (e.g., dust, cat, mouse, grass) can unpredictably lead intense clinical reactions. Furthermore, potential therapeutic approaches targeting ATP-related enhancement reactions presented.

Язык: Английский

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Activation of the receptor KIT induces the secretion of exosome‐like small extracellular vesicles

Journal of Extracellular Biology, Год журнала: 2024, Номер 3(1)

Опубликована: Янв. 1, 2024

Abstract The receptor tyrosine kinase (RTK) KIT and its ligand stem cell factor (SCF) are essential for human mast (huMC) survival proliferation. HuMCs expressing oncogenic variants secrete large numbers of extracellular vesicles (EVs). role plays in regulating EV secretion has not been examined. Here, we investigated the effects stimulation or inhibition activity on small EVs (sEVs). In huMCs constitutively active KIT, quantity quality secreted sEVs positively correlated with status KIT. SCF‐mediated murine MCs, transiently expressed HeLa cells, enhanced release exosome markers. contrast, ligand‐mediated RTK EGFR cells did affect sEV secretion. induced by either ligand‐activated was remarkably decreased when were treated inhibitors, concomitant reduced markers sEVs. Similarly, signalling kinases like PI3K, MAPK significantly Thus, activation early cascades stimulate exosome‐like a regulated fashion, which may have implications KIT‐driven functions.

Язык: Английский

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