MK2/3 Are Pivotal for IL-33–Induced and Mast Cell–Dependent Leukocyte Recruitment and the Resulting Skin Inflammation
| Autor: | Jan Dudeck, Ralf Stumm, Norman Häfner, Isabel Meininger, Sebastian Drube, Christiane Göpfert, Anna-Lena Müller, Anne Dudeck, Ingo M. Irmler, Matthias Gaestel, Mandy Beyer, Franziska Weber, Dagmar Schütz, Florian Kraft, Thomas Kamradt, Tatiana Yakovleva |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAP Kinase Signaling System p38 mitogen-activated protein kinases Immunology Inflammation Protein Serine-Threonine Kinases Biology Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Cell Movement In vivo Leukocytes medicine Animals Psoriasis Immunology and Allergy Mast Cells Cells Cultured Skin Mice Knockout Kinase Intracellular Signaling Peptides and Proteins Interleukin-33 Mast cell In vitro Cell biology Interleukin 33 030104 developmental biology medicine.anatomical_structure Inflammation Mediators medicine.symptom Stem cell 030215 immunology |
| Zdroj: | The Journal of Immunology. 197:3662-3668 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1600658 |
| Popis: | The IL-1R family member IL-33R mediates Fcε-receptor-I (FcεRI)-independent activation of mast cells leading to NF-κB activation and consequently the production of cytokines. IL-33 also induces the activation of MAPKs, such as p38. We aimed to define the relevance of the p38-targets, the MAPK-activated protein kinases 2 and 3 (MK2 and MK3) in IL-33-induced signaling and the resulting mast cell effector functions in vitro and in vivo. We demonstrate that the IL-33-induced IL-6 and IL-13 production strongly depends on the MK2/3-mediated activation of ERK1/2 and PI3K signaling. Furthermore, in the presence of the stem cell factors, IL-33 did induce an MK2/3-, ERK1/2- and PI3K-dependent production of TNF-α. In vivo, the loss of MK2/3 in mast cells decreased the IL-33-induced leukocyte recruitment and the resulting skin inflammation. Therefore, the MK2/3-dependent signaling in mast cells is essential to mediate IL-33-induced inflammatory responses. Thus, MK2/3 are potential therapeutic targets for suppression of IL-33-induced inflammation skin diseases such as psoriasis. |
| Databáze: | OpenAIRE |
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