RELMα Is Induced in Airway Epithelial Cells by Oncostatin M without Requirement of STAT6 or IL-6 in Mouse Lungs In Vivo
Resistin-like molecule alpha (RELMα) and YM-1 are secreted proteins implicated in murine models of alternatively activated macrophage (AA/M2) accumulation and Th2-skewed inflammation. Since the gp130 cytokine Oncostatin M (OSM) induces a Th2-like cytokine and AA/M2 skewed inflammation in mouse lung,...
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MDPI AG
2020-05-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/6/1338 |
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| author | Lilian Ho Ashley Yip Francis Lao Fernando Botelho Carl D. Richards |
| author_facet | Lilian Ho Ashley Yip Francis Lao Fernando Botelho Carl D. Richards |
| author_sort | Lilian Ho |
| collection | DOAJ |
| description | Resistin-like molecule alpha (RELMα) and YM-1 are secreted proteins implicated in murine models of alternatively activated macrophage (AA/M2) accumulation and Th2-skewed inflammation. Since the gp130 cytokine Oncostatin M (OSM) induces a Th2-like cytokine and AA/M2 skewed inflammation in mouse lung, we here investigated regulation of RELMα and YM-1. Transient pulmonary overexpression of OSM by Adenovirus vector (AdOSM) markedly induced RELMα and YM-1 protein expression in total lung. In situ hybridization showed that RELMα mRNA was highly induced in airway epithelial cells (AEC) and was co-expressed with CD68 mRNA in some but not all CD68+ cells in parenchyma. IL-6 overexpression (a comparator gp130 cytokine) induced RELMα, but at significantly lower levels. IL-6 (assessing IL-6<sup>−/−</sup> mice) was not required, nor was STAT6 (IL-4/13 canonical signalling) for AdOSM-induction of RELMα in AEC. AEC responded directly to OSM in vitro as assessed by pSTAT3 activation. RELMα-deficient mice showed similar inflammatory cell infiltration and cytokine responses to wt in response to AdOSM, but showed less accumulation of CD206+ AA/M2 macrophages, reduced induction of extracellular matrix gene mRNAs for COL1A1, COL3A1, MMP13, and TIMP1, and reduced parenchymal alpha smooth muscle actin. Thus, RELMα is regulated by OSM in AEC and contributes to extracellular matrix remodelling in mouse lung. |
| first_indexed | 2024-03-10T19:33:59Z |
| format | Article |
| id | doaj.art-b84623f2867249df9108a99e1c28d9a3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:33:59Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b84623f2867249df9108a99e1c28d9a32023-11-20T01:55:00ZengMDPI AGCells2073-44092020-05-0196133810.3390/cells9061338RELMα Is Induced in Airway Epithelial Cells by Oncostatin M without Requirement of STAT6 or IL-6 in Mouse Lungs In VivoLilian Ho0Ashley Yip1Francis Lao2Fernando Botelho3Carl D. Richards4McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8P, CanadaMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8P, CanadaMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8P, CanadaMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8P, CanadaMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8P, CanadaResistin-like molecule alpha (RELMα) and YM-1 are secreted proteins implicated in murine models of alternatively activated macrophage (AA/M2) accumulation and Th2-skewed inflammation. Since the gp130 cytokine Oncostatin M (OSM) induces a Th2-like cytokine and AA/M2 skewed inflammation in mouse lung, we here investigated regulation of RELMα and YM-1. Transient pulmonary overexpression of OSM by Adenovirus vector (AdOSM) markedly induced RELMα and YM-1 protein expression in total lung. In situ hybridization showed that RELMα mRNA was highly induced in airway epithelial cells (AEC) and was co-expressed with CD68 mRNA in some but not all CD68+ cells in parenchyma. IL-6 overexpression (a comparator gp130 cytokine) induced RELMα, but at significantly lower levels. IL-6 (assessing IL-6<sup>−/−</sup> mice) was not required, nor was STAT6 (IL-4/13 canonical signalling) for AdOSM-induction of RELMα in AEC. AEC responded directly to OSM in vitro as assessed by pSTAT3 activation. RELMα-deficient mice showed similar inflammatory cell infiltration and cytokine responses to wt in response to AdOSM, but showed less accumulation of CD206+ AA/M2 macrophages, reduced induction of extracellular matrix gene mRNAs for COL1A1, COL3A1, MMP13, and TIMP1, and reduced parenchymal alpha smooth muscle actin. Thus, RELMα is regulated by OSM in AEC and contributes to extracellular matrix remodelling in mouse lung.https://www.mdpi.com/2073-4409/9/6/1338Oncostatin MRELMαairway epithelial cellslung inflammation |
| spellingShingle | Lilian Ho Ashley Yip Francis Lao Fernando Botelho Carl D. Richards RELMα Is Induced in Airway Epithelial Cells by Oncostatin M without Requirement of STAT6 or IL-6 in Mouse Lungs In Vivo Cells Oncostatin M RELMα airway epithelial cells lung inflammation |
| title | RELMα Is Induced in Airway Epithelial Cells by Oncostatin M without Requirement of STAT6 or IL-6 in Mouse Lungs In Vivo |
| title_full | RELMα Is Induced in Airway Epithelial Cells by Oncostatin M without Requirement of STAT6 or IL-6 in Mouse Lungs In Vivo |
| title_fullStr | RELMα Is Induced in Airway Epithelial Cells by Oncostatin M without Requirement of STAT6 or IL-6 in Mouse Lungs In Vivo |
| title_full_unstemmed | RELMα Is Induced in Airway Epithelial Cells by Oncostatin M without Requirement of STAT6 or IL-6 in Mouse Lungs In Vivo |
| title_short | RELMα Is Induced in Airway Epithelial Cells by Oncostatin M without Requirement of STAT6 or IL-6 in Mouse Lungs In Vivo |
| title_sort | relmα is induced in airway epithelial cells by oncostatin m without requirement of stat6 or il 6 in mouse lungs in vivo |
| topic | Oncostatin M RELMα airway epithelial cells lung inflammation |
| url | https://www.mdpi.com/2073-4409/9/6/1338 |
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