Mast Cells Expression of the ADAM-10 Protease is Inhibited BY IL-10 and TGFb1 (91.13)

Abstract

Abstract Asthma is an inflammatory lung disease that is caused in part by mast cell activation via IgE and antigen. B cell-mediated IgE secretion is suppressed by the low affinity IgE receptor, CD23. Recent data have demonstrated that CD23 function can be blocked by its cleavage with the protease ADAM-10. We demonstrate that mouse mast cells abundantly express surface ADAM-10 in vitro and in vivo. ADAM-10 surface expression is suppressed by the cytokines IL-10 and TGFb1, with approximately 50% inhibition after 3 days of culture. IL-10-mediated effects were Stat3-dependent and correlated with reduced ADAM-10 mRNA. These data suggest that IL-10 and TGFb1 may suppress allergic disease in part by reducing the effects of ADAM-10, allowing for CD23-mediated negative feedback. Supported by NIH grants 1R01 AI59638 and U19A1077435.