Carnosic acid inhibits the secretion of pro-inflammatory mediators in IL-33 activated mast cells 3750

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)