| First Author | Ho L | Year | 2020 |
| Journal | Cells | Volume | 9 |
| Issue | 6 | PubMed ID | 32471168 |
| Mgi Jnum | J:304398 | Mgi Id | MGI:6514495 |
| Doi | 10.3390/cells9061338 | Citation | Ho L, et al. (2020) RELMalpha is Induced in Airway Epithelial Cells by Oncostatin M Without Requirement of STAT6 or IL-6 in Mouse Lungs In Vivo. Cells 9(6):1338 |
| abstractText | Resistin-like molecule alpha (RELMalpha) 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 RELMalpha and YM-1. Transient pulmonary overexpression of OSM by Adenovirus vector (AdOSM) markedly induced RELMalpha and YM-1 protein expression in total lung. In situ hybridization showed that RELMalpha 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 RELMalpha, but at significantly lower levels. IL-6 (assessing IL-6(-)(/)(-) mice) was not required, nor was STAT6 (IL-4/13 canonical signalling) for AdOSM-induction of RELMalpha in AEC. AEC responded directly to OSM in vitro as assessed by pSTAT3 activation. RELMalpha-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, RELMalpha is regulated by OSM in AEC and contributes to extracellular matrix remodelling in mouse lung. |
