IL-33 priming amplifies ATP-mediated mast cell cytokine production
| Autor: | David B. Straus, Destiny Pryor, Tamara T. Haque, Sydney A. Kee, Jordan M. Dailey, Kaitlyn G. Jackson, Brian O. Barnstein, John J. Ryan |
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| Rok vydání: | 2022 |
| Předmět: |
Inflammation
Mice Inbred BALB C NFATC Transcription Factors Calcineurin Macrophages Immunology Peritonitis Interleukin-33 Cell Degranulation Eosinophils Mice Inbred C57BL Mice Adenosine Triphosphate Alarmins Animals Cytokines RNA Interference Mast Cells Receptors Purinergic P2X7 RNA Small Interfering Cells Cultured |
| Zdroj: | Cellular Immunology. 371:104470 |
| ISSN: | 0008-8749 |
| DOI: | 10.1016/j.cellimm.2021.104470 |
| Popis: | Inflammatory responses are required to block pathogen infection but can also lead to hypersensitivity and chronic inflammation. Barrier tissues actively release IL-33, ATP, and other alarmins during cell stress, helping identify pathogenic stimuli. However, it is unclear how these signals are integrated. Mast cells are critical initiators of allergic inflammation and respond to IL-33 and ATP. We found that mouse mast cells had a 3-6-fold increase in ATP-induced cytokine production when pre-treated with IL-33. This effect was observed at ATP concentrations 100 µM and required 30-minute IL-33 exposure. ATP-induced degranulation was not enhanced by pretreatment nor was the response to several pathogen molecules. Mechanistic studies implicated the P2X7 receptor and calcineurin/NFAT pathway in the enhanced ATP response. Finally, we found that IL-33 + ATP co-stimulation enhanced peritoneal eosinophil and macrophage recruitment. These results support the hypothesis that alarmins collaborate to surpass a threshold necessary to initiate an inflammatory response. |
| Databáze: | OpenAIRE |
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