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Novel MRGPRX2 antagonists inhibit IgE-independent activation of human umbilical cord blood-derived mast cells.

08:00 EDT 12th July 2019 | BioPortfolio

Summary of "Novel MRGPRX2 antagonists inhibit IgE-independent activation of human umbilical cord blood-derived mast cells."

Human MCs are primary effectors implicated in immune surveillance and defense by secreting histamine and various inflammatory mediators, a mechanism termed as degranulation. MCs can be activated by two pathways: IgE-dependent classical pathway and the IgE-independent pathway that utilizes various cationic molecules including substance P (SP) and pituitary adenylate cyclase-activating polypeptides, which are host defense peptides collectively known as basic secretagogues. Our pharmacological study investigated whether or not IgE-independent MC activation is mediated via MRGPRX2. We identified two novel MRGPRX2 antagonists, which completely inhibited the degranulation of human cord blood-derived MCs (hCMCs) induced by basic secretagogues and pseudoallergic drug, icatibant, but IgE- or A23187-challenged hCMCs were resistant to MRGPRX2 antagonists. The MRGPRX2 antagonists markedly inhibited the de novo synthesis of SP-induced prostaglandin D in hCMCs. Moreover, the antagonists were able to inhibit p42/44 mitogen-activated protein kinase signal in hCMCs activated by SP. This study strongly suggests that MRGPRX2 antagonists may be a promising drug to prevent the IgE-independent allergic reactions, and thus, MRGPRX2 antagonist development may lead to a promising therapeutic medication for the IgE-independent allergic reactions.

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This article was published in the following journal.

Name: Journal of leukocyte biology
ISSN: 1938-3673
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Compounds that bind to and inhibit the activation of ANDROGEN RECEPTORS.

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