Carnosic acid inhibits mast cell pro‐inflammatory mediator release in allergic inflammation
Notice bibliographique
Résumé
Over the past several decades, developed countries have been plagued by the increasing prevalence of allergic disorders. This allergy epidemic has led to an exponential increase in health care‐associated costs, while significantly deteriorating quality of life for those affected. Allergic inflammation is a consequence of an excessive and undesirable immune response towards environmental allergens, mediated by immune sentinels known as mast cells. Mast cells are ubiquitously distributed in vascularized tissues, where they play an essential role in host defence, in addition to pathological contexts of inflammation. Allergen detection by the immune system results in IgE‐mediated mast cell activation, characterized by rapid degranulation during the early phase, and sustained release of newly synthesized pro‐inflammatory mediators in the late phase. Plant derived micronutrients, known as polyphenols, have been explored as therapeutic options in pathological models, due to the modulatory effects they have on pro‐inflammatory mediator release. We have recently established rosemary extract (RE); a mixture abundant in polyphenolic compounds, as a potent inhibitor of mast cell mediated allergic inflammation, through attenuation of essential signalling cascades required for pro‐inflammatory mediator secretion. The objective of this study was to evaluate the therapeutic potential of three major polyphenolic constituents of RE including: carnosic acid (CA), carnosol (CO), and rosmarinic acid (RA), assessing the ability of isolated polyphenols to inhibit pro‐inflammatory mediator release following mast cell activation. Bone marrow‐derived mast cells (BMMCs) were sensitized with IgE and stimulated with allergen, while simultaneously treated with various concentrations of CA, CO, or RA. Mast cell degranulation was measured via the β‐hexosaminidase release assay, while late phase pro‐inflammatory mediator release was quantified by enzyme‐linked immunosorbent assay. Following individual treatment with CA and CO, β‐hexosaminidase release was significantly inhibited dose‐dependently to 14% and 17% of control respectively (p < 0.001), while RA had no effect on β‐hexosaminidase release. ELISA analysis showed that CA significantly inhibited release of TNF (p<0.0001), IL‐6 (p<0.0001), IL‐13 (p<0.0001), CCL1 (p<0.001), and CCL2 (p<0.05), RA inhibited CCL2 (p<0.05), and treatment with CO did not inhibit the release of any cytokine examined. These results suggest that CA is a potent inhibitor of both the early and late phase of allergen‐induced mast cell activation. Further dissection of the mechanism behind CA mediated modulation of essential mast cell signalling and subsequent pro‐inflammatory mediator release will inform on its utility in regulation of mast cell function in numerous mast cell‐dependent inflammatory disorders. Support or Funding Information Supported by the Natural Sciences and Engineering Research Council of Canada (NSERC); Canada Foundation for Innovation (CFI); Government of Ontario; and Brock University.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».