IL-33による骨髄由来マスト細胞のプリン受容体発現に対する影響

抄録

Interleukin (IL)-33 is constitutively expressed in the nucleus of various cell types and released into extracellular fluid by cytotoxicity. IL-33 has been shown to exacerbate allergic diseases by activation of mast cells. Recently, we demonstrated that extracellular ATP enhanced mast cell activation by both antigen-dependent and independent mechanisms. In this study we investigated whether IL-33 stimulation affects P2 receptor-mediated mast cell responses. Stimulation of bone marrow-derived mast cell (BMMC) with IL-33 neither induced degranulation by itself nor altered the ATP-induced responses by co-stimulation with ATP. In contrast, pretreatment of BMMCs with IL-33 for 24 hour enhanced degranulation induced by high concentrations of ATP (hATP). The hATP-induced degranulation was inhibited by P2X7 receptor antagonist. Furthermore, IL-33 pretreatment increased the P2X7 receptor mRNA levels in BMMCs. FACS analysis confirmed an increase in BMMC cell surface P2X7 receptor expression by pretreatment with IL-33. Since activation of mast cells by P2X7 receptor has been reported to exacerbate allergic inflammation, current results suggest that increased expression of P2X7 receptors in mast cells contributes to the exacerbation of allergic disease caused by IL-33.