IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M
The interleukin-1 family member IL-33 participates in both innate and adaptive T helper-2 immune cell responses in models of lung disease. The IL-6-type cytokine Oncostatin M (OSM) elevates lung inflammation, Th2-skewed cytokines, alternatively activated (M2) macrophages, and eosinophils in C57Bl/6...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/4087315 |
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| author | Fernando Botelho Anisha Dubey Ehab A. Ayaub Rex Park Ashley Yip Allison Humbles Roland Kolbeck Carl D. Richards |
| author_facet | Fernando Botelho Anisha Dubey Ehab A. Ayaub Rex Park Ashley Yip Allison Humbles Roland Kolbeck Carl D. Richards |
| author_sort | Fernando Botelho |
| collection | DOAJ |
| description | The interleukin-1 family member IL-33 participates in both innate and adaptive T helper-2 immune cell responses in models of lung disease. The IL-6-type cytokine Oncostatin M (OSM) elevates lung inflammation, Th2-skewed cytokines, alternatively activated (M2) macrophages, and eosinophils in C57Bl/6 mice in vivo. Since OSM induces IL-33 expression, we here test the IL-33 function in OSM-mediated lung inflammation using IL-33-/- mice. Adenoviral OSM (AdOSM) markedly induced IL-33 mRNA and protein levels in wild-type animals while IL-33 was undetectable in IL-33-/- animals. AdOSM treatment showed recruitment of neutrophils, eosinophils, and elevated inflammatory chemokines (KC, eotaxin-1, MIP1a, and MIP1b), Th2 cytokines (IL-4/IL-5), and arginase-1 (M2 macrophage marker) whereas these responses were markedly diminished in IL-33-/- mice. AdOSM-induced IL-33 was unaffected by IL-6-/- deficiency. AdOSM also induced IL-33R+ ILC2 cells in the lung, while IL-6 (AdIL-6) overexpression did not. Flow-sorted ILC2 responded in vitro to IL-33 (but not OSM or IL-6 stimulation). Matrix remodelling genes col3A1, MMP-13, and TIMP-1 were also decreased in IL-33-/- mice. In vitro, IL-33 upregulated expression of OSM in the RAW264.7 macrophage cell line and in bone marrow-derived macrophages. Taken together, IL-33 is a critical mediator of OSM-driven, Th2-skewed, and M2-like responses in mouse lung inflammation and contributes in part through activation of ILC2 cells. |
| format | Article |
| id | doaj-art-13b27e8ec6de4da39d57ceafb167da4f |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-13b27e8ec6de4da39d57ceafb167da4f2025-02-03T01:20:30ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/40873154087315IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin MFernando Botelho0Anisha Dubey1Ehab A. Ayaub2Rex Park3Ashley Yip4Allison Humbles5Roland Kolbeck6Carl D. Richards7McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 3Z5, CanadaMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 3Z5, CanadaDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USAMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 3Z5, CanadaMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 3Z5, CanadaEarly RIA, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0WG, UKEarly RIA, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USAMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, L8N 3Z5, CanadaThe interleukin-1 family member IL-33 participates in both innate and adaptive T helper-2 immune cell responses in models of lung disease. The IL-6-type cytokine Oncostatin M (OSM) elevates lung inflammation, Th2-skewed cytokines, alternatively activated (M2) macrophages, and eosinophils in C57Bl/6 mice in vivo. Since OSM induces IL-33 expression, we here test the IL-33 function in OSM-mediated lung inflammation using IL-33-/- mice. Adenoviral OSM (AdOSM) markedly induced IL-33 mRNA and protein levels in wild-type animals while IL-33 was undetectable in IL-33-/- animals. AdOSM treatment showed recruitment of neutrophils, eosinophils, and elevated inflammatory chemokines (KC, eotaxin-1, MIP1a, and MIP1b), Th2 cytokines (IL-4/IL-5), and arginase-1 (M2 macrophage marker) whereas these responses were markedly diminished in IL-33-/- mice. AdOSM-induced IL-33 was unaffected by IL-6-/- deficiency. AdOSM also induced IL-33R+ ILC2 cells in the lung, while IL-6 (AdIL-6) overexpression did not. Flow-sorted ILC2 responded in vitro to IL-33 (but not OSM or IL-6 stimulation). Matrix remodelling genes col3A1, MMP-13, and TIMP-1 were also decreased in IL-33-/- mice. In vitro, IL-33 upregulated expression of OSM in the RAW264.7 macrophage cell line and in bone marrow-derived macrophages. Taken together, IL-33 is a critical mediator of OSM-driven, Th2-skewed, and M2-like responses in mouse lung inflammation and contributes in part through activation of ILC2 cells.http://dx.doi.org/10.1155/2020/4087315 |
| spellingShingle | Fernando Botelho Anisha Dubey Ehab A. Ayaub Rex Park Ashley Yip Allison Humbles Roland Kolbeck Carl D. Richards IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M Mediators of Inflammation |
| title | IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M |
| title_full | IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M |
| title_fullStr | IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M |
| title_full_unstemmed | IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M |
| title_short | IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M |
| title_sort | il 33 mediates lung inflammation by the il 6 type cytokine oncostatin m |
| url | http://dx.doi.org/10.1155/2020/4087315 |
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