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Article Publish Status: FREE
Abstract Title:

Carnosic acid inhibits secretion of allergic inflammatory mediators in IgE-activated mast cells via direct regulation of Syk activation.

Abstract Source:

J Biol Chem. 2023 Jan 3:102867. Epub 2023 Jan 3. PMID: 36608933

Abstract Author(s):

Robert W E Crozier, Michael Yousef, Jeremia M Coish, Val A Fajardo, Evangelia Tsiani, Adam J MacNeil

Article Affiliation:

Robert W E Crozier

Abstract:

Mast cells are essential regulators of inflammation most recognized for their central role in allergic inflammatory disorders. Signaling via the high-affinity immunoglobulin E (IgE) receptor, FcεRI, leads to rapid degranulation of preformed granules and the sustained release of newly-synthesized pro-inflammatory mediators. Our group recently established rosemary extract (RE) as a potent regulator of mast cell functions, attenuating MAPK and NF-κB signaling. Carnosic acid (CA)-a major polyphenolic constituent of RE-has been shown to exhibit anti-inflammatory effects in other immune cell models, but its role as a potential modulator of mast cell activation is undefined. Therefore, we sought here to determine the modulatory effects of CA in a mast cell model of allergic inflammation. We sensitized bone marrow-derived mast cells (BMMCs) with anti-trinitrophenyl (TNP) IgE and activated with allergen (TNP-BSA) under stem cell factor (SCF) potentiation, in addition to treatment with CA. Our results indicate that CA significantly inhibits allergen-induced early phase responses including Camobilization, ROS production, and subsequent degranulation. We also show CA treatment reduced late phase responses, including the release of all cytokines and chemokines examined following IgE stimulation, and corresponding gene expression excepting that of CCL2. Importantly, we determined that CA mediates its inhibitory effects through modulation of tyrosine kinase Syk and downstream effectors TAK1 (Ser412) and Akt (Ser473) as well as NF-κB signaling, while phosphorylation of FcεRI (γchain) and MAPK proteins remained unaltered. These novel findings establish CA as a potent modulator of mast cell activation, warranting further investigation as a putative anti-allergy therapeutic.

Study Type : In Vitro Study

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