IL-33-mediated Mast Cell Function is Female Dominant 2259527

Abstract

Abstract Introduction Allergic asthma is more common and severe in women than in men. One component of allergic inflammation is IL-33, a cytokine released by the airway epithelium when damaged by allergens. Methods We used mouse bone marrow-derived mast cells for in vitro analysis of IL-33-induced cytokine production, inflammatory lipid secretion, and signal transduction. We also performed in vivo analysis of IL-33-induced peritonitis. Results Using both in vitro and in vivo models of IL-33-mediated inflammation, we found that IL-33 effects are more prominent in females. We show that mast cells cultured from female C57BL/6 or C3H/HeJ mice produce stronger IL-33-induced cytokines than matched male cultures. We also demonstrate that female-dominant responses include arachidonic acid metabolites. Importantly, we reveal that IL-33-mediated JNK activation is heightened in female mast cells. Surprisingly, ERK activation is greater in male mast cells. Conclusion Overall, these data support the hypothesis that specific cell signaling differences contribute to the female-dominant IL-33 response. Funding Source NIH 1R01AI164710 Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)