The role of 1a,25-dihydroxyvitamin D3 in IgE-mediated mast cell activation (HYP4P.313)

Abstract

Abstract As the prevalence of allergic diseases such as allergic asthma and rhinitis continues to increase, there is growing interest in novel approaches to blunt the inflammatory processes. IgE-mediated mast cell activation results in the release of histamine and other inflammatory mediators. Vitamin D has been linked to allergic disease, with vitamin D deficiency being linked to increased risk for development and severity of allergic disease. We assessed the effects of the Vitamin D metabolite 1a,25-dihydroxyvitamin D3 (1,25D3) on IgE-mediated mast cell activation in vitro. We find that 1,25D3 suppresses IgE-mediated inflammatory cytokine and chemokine production. Surprisingly, these effects do not require expression of the canonical receptor for 1,25D3 (VDR), as wild type and VDR KO mast cells are similarly suppressed by 1,25D3. Additionally, these effects appear to be somewhat stimulus-specific, as IL-33-mediated mast cell activation s not inhibited by 1,25D3. We postulate that the chaperone protein Pdia3, an alternative plasma membrane-associated receptor for 1,25D3, may be responsible for the VDR-independent, anti-inflammatory effects on IgE-mediated mast cell activation. Our data depict novel evidence that 1,25D3 can attenuate the pro-inflammatory mast cell response, and emphasize the possible utility of vitamin D supplementation for treatment of allergic and inflammatory diseases.