IL-33 is processed into mature bioactive forms by neutrophil serine proteases (172.26)
| Autor: | Emma Lefrançais, Stéphane Roga, Violette Gautier, Anne Gonzales de Peredo, Bernard Monsarrat, Jean Philippe Girard, Corinne Cayrol |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:172.26-172.26 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.188.supp.172.26 |
| Popis: | IL-33 is a chromatin-associated nuclear cytokine from the IL-1 family, which has been linked to many inflammatory diseases. IL-33 signals through the receptor ST2 and drives production of cytokines in innate effector cells and T helper type 2 lymphocytes. IL-33 is constitutively expressed in the nuclei of endothelial cells and in epithelial cells of tissues exposed to the environment. It was initially believed that IL-33, like IL-1β and IL-18, requires processing by caspase-1 for biological activity. On the contrary, we reported that full length IL-33 is biologically active, and that processing by apoptotic caspases results in IL-33 inactivation, rather than activation. We also found that full length IL-33 is released upon cellular damage and we proposed that IL-33 may function, similarly to HMGB1, as an endogenous danger signal. Because IL-33 plays important roles in inflammatory diseases, we hypothesized that IL-33 could be cleaved by proteases released during inflammation. We analyzed the effects of inflammatory proteases from innate effector cells, on IL-33 processing and biological activity. We found that IL-33 can be cleaved and activated by several inflammatory proteases. Interestingly, all forms generated by these proteases are “super-active” IL-33 forms that contain an intact IL1-like cytokine domain. We propose that the inflammatory microenvironment exacerbates disease-associated functions of IL-33 through the generation of “super-active” IL-33 forms. |
| Databáze: | OpenAIRE |
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