Inflammasome activation and IL-1ß target IL-1a for secretion as opposed to surface expression
| Autor: | Gabriela Senti, Lars E. French, Pål Johansen, Hans-Dietmar Beer, Annette Oxenius, Emmanuel Contassot, Antonia Fettelschoss, Salomé LeibundGut-Landmann, Magdalena Kistowska, Martin F. Bachmann, Thomas M. Kündig |
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| Přispěvatelé: | University of Zurich, Fettelschoss-Gabriel, Antonia |
| Rok vydání: | 2011 |
| Předmět: |
Interleukin-1beta
Caspase 1 610 Medicine & health Inflammation Biology Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Interleukin-1alpha medicine Animals Secretion Receptor 030304 developmental biology 1000 Multidisciplinary 0303 health sciences Multidisciplinary Innate immune system 10177 Dermatology Clinic Inflammasome 11359 Institute for Regenerative Medicine (IREM) Biological Sciences Flow Cytometry Cell biology 570 Life sciences biology medicine.symptom 030215 immunology medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| DOI: | 10.1073/pnas.1109176108 |
| Popis: | Interleukin-1α (IL-1α) and -β both bind to the same IL-1 receptor (IL-1R) and are potent proinflammatory cytokines. Production of proinflammatory (pro)–IL-1α and pro–IL-1β is induced by Toll-like receptor (TLR)-mediated NF-κB activation. Additional stimulus involving activation of the inflammasome and caspase-1 is required for proteolytic cleavage and secretion of mature IL-1β. The regulation of IL-1α maturation and secretion, however, remains elusive. IL-1α exists as a cell surface-associated form and as a mature secreted form. Here we show that both forms of IL-1α, the surface and secreted form, are differentially regulated. Surface IL-1α requires NF-κB activation only, whereas secretion of mature IL-1α requires additional activation of the inflammasome and caspase-1. Surprisingly, secretion of IL-1α also required the presence of IL-1β, as demonstrated in IL-1β–deficient mice. We further demonstrate that IL-1β directly binds IL-1α, thus identifying IL-1β as a shuttle for another proinflammatory cytokine. These results have direct impact on selective treatment modalities of inflammatory diseases. |
| Databáze: | OpenAIRE |
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