Type I Interferon Signaling is Required for Oncostatin-M Driven Inflammatory Responses in Mouse Lung.
Kyle MacDonaldFernando BotelhoAli A AshkarCarl D RichardsPublished in: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (2022)
Type I interferons (IFNs) consist of a group of structurally similar cytokines that play an integral role in regulating the immune response to combat lung infections. In certain models type I IFNs have also been associated with suppression of Th2-skewed immune and inflammatory responses. Transient pulmonary overexpression of the gp130 cytokine Oncostatin M (OSM) by Adenovirus vector (AdOSM) induces a robust Th2-skewed cytokine/inflammatory profile in C57Bl/6 murine lungs. In this study we assessed type I IFN function in OSM-mediated inflammation in vivo using Ifnar1 -/- C57Bl/6 mice and Ifnar1 -deficient cells in vitro . Ifnar1 -/- mice showed a significant reduction in AdOSM-induced histopathology (epithelial hyperplasia, alveolar septal wall thickening, cellular infiltration), and levels of IL-6 and chemokine protein (CXCL-1/KC and CCL24/eotaxin-2) in lungs compared with wild-type. Ifnar1 -/- murine fibroblasts and human type I IFN receptor ( Ifnar )-knockdown fibroblasts were also less responsive to OSM in STAT3 activation and cytokine production compared with Ifnar -sufficient cells in vitro . Exogenous type I IFN induced IL-6 responses in mouse and human fibroblasts and in combination with OSM further stimulated IL-6 production, suggesting a concerted action of type I IFNs and OSM. Taken together, these results demonstrate that cross-talk between IFNAR and OSM signaling enhances cell responses and modulates OSM-driven responses in lung inflammation.
Keyphrases
- wild type
- induced apoptosis
- endothelial cells
- oxidative stress
- dendritic cells
- high glucose
- immune response
- diabetic rats
- cell cycle arrest
- drug induced
- extracellular matrix
- high fat diet induced
- liver injury
- heart failure
- transcription factor
- endoplasmic reticulum stress
- single cell
- signaling pathway
- type diabetes
- metabolic syndrome
- mesenchymal stem cells
- cancer therapy
- gene therapy
- skeletal muscle
- atrial fibrillation