Oncostatin M Counteracts the Fibrotic Effects of TGF-β1 and IL-4 on Nasal-Polyp-Derived Fibroblasts: A Control of Fibrosis in Chronic Rhinosinusitis with Nasal Polyps?

Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with inflammation and tissue remodeling including myofibroblasts differentiation and extracellular matrix (ECM) deposition mediated by TGF-beta 1 and IL-4. Oncostatin M (OSM) is a cytokine involved in fibrotic processes in other cellular subtypes. We investigated the mechanisms of action of OSM in the fibrosis process associated with CRSwNP. The expression of IL-4, OSM and TGF-beta 1 was assessed by RT-qPCR. Primary human cultures of nasal-polyp-derived fibroblasts were established and stimulated by TGF-beta 1 and/or IL-4 and/or OSM. The expression of ECM components and alpha SMA was determined by RT-qPCR and Western blot. TGF-beta 1-Smad3 signaling was investigated by immunofluorescence. TGF-beta 1, IL-4 and OSM as well as alpha SMA were overexpressed in nasal polyps when compared to noninflammatory nasal mucosa. In TGF-beta 1-stimulated nasal-polyp-derived fibroblasts, ECM genes and alpha SMA gene and protein were overexpressed, as well as alpha SMA in IL-4-stimulated fibroblasts. OSM counteracted the profibrotic effect of TGF-beta 1 on ECM components and alpha SMA. TGF-beta 1-induced nuclear translocation of Smad3 was completely reversed by OSM. OSM counteracts the profibrotic effect of IL-4 and also TGF-beta 1, by inhibiting the nuclear translocation of Smad3. We suggest OSM could be an efficient tool to protect against fibrosis in CRSwNP.

Automated summary

This study investigated the mechanisms of action of Oncostatin M (OSM) in the fibrosis process associated with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). The results showed that OSM can counteract the profibrotic effects of TGF-beta 1 and IL-4 by inhibiting nuclear translocation of Smad3. Therefore, OSM could be an efficient tool to protect against fibrosis in CRSwNP.