Introduction
Mast cells, key effector cells of allergic and innate immune responses, have recently been reported to be an important source of IL-1ß in patients with autoinflammatory conditions such as cryopyrin-associated-periodic-fever syndromes (CAPS). CAPS patients show IL-1beta-driven systemic inflammation together with non-histamine dependent urticarial rash, which are caused by activating mutations of the inflammasome, a multiprotein oligomer responsible for the initiation of inflammatory responses to pathogens.
Objectives
To determine if mast cells can produce and release IL-1ß in response to pathogenic signals that target the inflammasomes NLRP3, NLRC4, or AIM2.
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Methods
Peritoneal mast cells (PMCs) were obtained through lavage from adult (>8 weeks) C57BL/6 mice and WBB6F1 Kit+/+ mice, purified via CD117+ bead selection (>96 % purity) and cultured for 7-14 days. 105 cells/well were primed with LPS (100ng/ml) for 15 hrs. Then the PMCs were stimulated with 10 µM Nigericin (NLRP3), 5mM ATP (NLRP3), 100µM R837 (NLRP3) for 45 min or for 4 hours with 600 ng Flagellin (NLRC4) transfected with DOTAP or 200 ng polydAdT (AIM2) transfected with Lipofectamine. IL-1 beta production was measured in the supernatants by Elisa.
Results
PMCs produced significant amounts (mean ± SEM) of IL-1ß upon stimulation with Nigericin (467 ± 41pg/ml), ATP (152 ± 88pg/ml), R837 (21 ± 2 pg/ml), Flagellin (245 ± 44pg/ml) and polydAdT (571 ± 194pg/ml) as compared to no stimuli (7,1 ± 0,8 pg/ml) only.
Conclusion
We show that mouse mast cells incubated with inflammasome activators produce significant amounts of IL-1ß ex vivo. Our data suggest that inflammasome-driven mast cell activation and subsequent IL-1ß production and release may importantly contribute to innate immune responses to pathogens.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Competing interests
None declared.