Treatment with carnosic acid during mast cell differentiation modulates the mature mast cell phenotype and inflammatory response 3847

Description Hematopoietic progenitors from the bone marrow home to and are conditioned by the local milieu in the periphery in the development of tissue resident mast cells. Due to their long-lived nature, strategies altering the inflammatory capacity of mast cells are attractive in therapeutic considerations for mast cell-driven inflammatory disorders, including allergy. Carnosic acid (CA) has been previously demonstrated by our group to attenuate inflammatory mast cell responses when applied during acute mast cell activation. We therefore sought to determine if CA influences the inflammatory capacity of mast cells when applied during differentiation. Bone marrow-derived mast cells (BMMCs) were generated from C57BL/6 mice and cultured twice weekly under the influence of IL-3, with or without CA. CA was found to profoundly reduce cell surface levels of key mast cell receptors c-kit and ST2. Allergen-induced early and late phase responses were assessed after stimulation of IgE-sensitized BMMCs with allergen (TNP-BSA) and SCF. CA was found to abrogate early phase degranulation and reduce cell surface levels of the exocytosis marker CD63. Late phase mediator release was differentially regulated, as CA impaired the release of IL-13 and CCL2, while enhancing the release of CCL1 and CCL3. CA was further found to exacerbate ST2-dependent mediator release induced by IL-33. These findings position CA as a potential modulator of mast cell activity when applied during the differentiation period. Funding Sources Supported by the NSERC discovery grant, Canadian Foundation for Innovation, the Ontario government (Ontario Graduate Scholarship) and Brock University.