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?

Autor: Carsuzaa F; Laboratoire Inflammation Tissus Epithéliaux et Cytokines (LITEC), UR15560, Université de Poitiers, 86000 Poitiers, France.; Service ORL, Chirurgie Cervico-Maxillo-Faciale et Audiophonologie, Centre Hospitalier Universitaire de Poitiers, 86000 Poitiers, France., Béquignon É; Service ORL et Chirurgie Cervico-Faciale, Centre Hospitalier Intercommunal de Créteil, 94000 Créteil, France.; Laboratoire INSERM UMR955 Eq13, Institut Mondor de Recherche Biomédicale, 94000 Créteil, France., Bainaud M; Laboratoire Inflammation Tissus Epithéliaux et Cytokines (LITEC), UR15560, Université de Poitiers, 86000 Poitiers, France.; Service Immunologie et Inflammation, Centre Hospitalier Universitaire de Poitiers, 86021 Poitiers, France., Jégou JF; Laboratoire Inflammation Tissus Epithéliaux et Cytokines (LITEC), UR15560, Université de Poitiers, 86000 Poitiers, France., Dufour X; Laboratoire Inflammation Tissus Epithéliaux et Cytokines (LITEC), UR15560, Université de Poitiers, 86000 Poitiers, France.; Service ORL, Chirurgie Cervico-Maxillo-Faciale et Audiophonologie, Centre Hospitalier Universitaire de Poitiers, 86000 Poitiers, France., Lecron JC; Laboratoire Inflammation Tissus Epithéliaux et Cytokines (LITEC), UR15560, Université de Poitiers, 86000 Poitiers, France.; Service Immunologie et Inflammation, Centre Hospitalier Universitaire de Poitiers, 86021 Poitiers, France., Favot L; Laboratoire Inflammation Tissus Epithéliaux et Cytokines (LITEC), UR15560, Université de Poitiers, 86000 Poitiers, France.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Jun 04; Vol. 23 (11). Date of Electronic Publication: 2022 Jun 04.
DOI: 10.3390/ijms23116308
Abstrakt: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with inflammation and tissue remodeling including myofibroblasts differentiation and extracellular matrix (ECM) deposition mediated by TGF-β1 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-β1 was assessed by RT-qPCR. Primary human cultures of nasal-polyp-derived fibroblasts were established and stimulated by TGF-β1 and/or IL-4 and/or OSM. The expression of ECM components and αSMA was determined by RT-qPCR and Western blot. TGF-β1-Smad3 signaling was investigated by immunofluorescence. TGF-β1, IL-4 and OSM as well as αSMA were overexpressed in nasal polyps when compared to noninflammatory nasal mucosa. In TGF-β1-stimulated nasal-polyp-derived fibroblasts, ECM genes and αSMA gene and protein were overexpressed, as well as αSMA in IL-4-stimulated fibroblasts. OSM counteracted the profibrotic effect of TGF-β1 on ECM components and αSMA. TGF-β1-induced nuclear translocation of Smad3 was completely reversed by OSM. OSM counteracts the profibrotic effect of IL-4 and also TGF-β1, by inhibiting the nuclear translocation of Smad3. We suggest OSM could be an efficient tool to protect against fibrosis in CRSwNP.
Databáze: MEDLINE
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