Cross-linking IgE with antigen induces proinflammatory cytokine production via inflammasome signaling

Introduction and objective of study: Mast cells play a crucial role in acute and allergic inflammation, and have high-affinity receptors for IgE (FcRI) on their surface. Cross-linking of surface IgE molecules results in exocytosis of pre-formed mediators such as proinflammatory cytokines. In response to injurious or infectious agents caspase-1 activating multiprotein complexes, termed inflammasomes, assemble in the cytoplasm of cells. Activated caspase-1 cleaves the proforms of the interleukin-1 cytokine family members leading to their activation and secretion. Not much in known on the role of inflammasome and caspase-1 in mast cell function. In this study, we investigated the role of inflammasome/caspase-1 on degranulation and cytokine release of mast cells. Materials and methods: In mouse mast cells, derived from a culture of bone marrow cells (BMMC) of male BALB/cBy the effect of inhibition of caspase-1 with a specific inhibitor (Z-VAD-FMK) was monitored by measuring tumor necrosis factoralpha and interleukin-6 production and degranulation. Results: In BMMC, we found that preincubation with anti-caspase-1 did not affect mast cell degranulation, however suppressed the release of cytokines induced by cross-linking IgE and antigen. Conclusion: This study indicates that in-flammasome signaling may directly or indirectly promote the production of IL-6 and TNF-alpha by activated mast cells.