Carnosic acid inhibits the secretion of pro-inflammatory mediators in IL-33 activated mast cells 3750
Bibliographic record
Abstract
Abstract Description Mast cells are immune sentinels enriched in tissues exposed to the external environment, such as the skin, lungs, and gut. They play important roles in both innate and adaptive immunity and are noted for their major role in allergic inflammation. Mast cells express high levels of ST2, the receptor for interleukin-33 (IL-33), an alarmin cytokine released in response to cellular injury. IL-33 binding to ST2 triggers mast cell activation, contributing to the pathogenesis of allergic and non-allergic inflammatory disorders. We recently demonstrated that carnosic acid (CA), a polyphenol derived from Rosmarinus officinalis L., significantly inhibits mast cell activation in the context of allergic inflammation. Building on this, we sought to explore the effects of CA on IL-33-mediated mast cell activation. CA treatment significantly reduced the release of pro-inflammatory mediators (IL-6, IL-13, TNF, CCL1, CCL2, CCL3) in bone marrow-derived mast cells stimulated with IL-33 in the presence or absence of allergen-mediated co-stimulation. Unexpectedly, CA treatment increased Akt and NFκB signaling following IL-33 activation, leading to elevated IL6, IL13 and CCL3 gene expression and intracellular protein levels of IL-6 and CCL3. These findings collectively suggest that CA impairs secretory mechanisms associated with IL-33-induced mast cell activation, further highlighting its potential as a therapeutic agent for managing allergies and other inflammatory diseases mediated by IL-33. Funding Sources Supported by the Canada Foundation for Innovation, Natural Sciences and Engineering Research Council of Canada (Discovery Grant and Canada Graduate Scholarship - Masters), Government of Ontario, and Brock University. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".