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?

被引：13
作者：
Carsuzaa, Florent [1 ,2 ]
Bequignon, Emilie [3 ,4 ]
Bainaud, Matthieu [1 ,5 ]
Jegou, Jean-Francois [1 ]
Dufour, Xavier [1 ,2 ]
Lecron, Jean-Claude [1 ,5 ]
Favot, Laure [1 ]
机构：
[1] Univ Poitiers, Lab Inflammat Tissus Epitheliaux & Cytokines LITE, UR15560, F-86000 Poitiers, France
[2] CHU Poitiers, Serv ORL Chirurg Cervicomaxillofaciale & Audiopho, F-86000 Poitiers, France
[3] Ctr Hosp Intercommunal Creteil, Serv ORL & Chirurg Cervicofaciale, F-94000 Creteil, France
[4] Inst Mondor Rech Biomed, Lab INSERM UMR955 Eq13, F-94000 Creteil, France
[5] CHU Poitiers, Serv Immunol & Inflammat, F-86073 Poitiers, France
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2022年 / 23卷 / 11期
关键词：
chronic rhinosinusitis; cytokines; inflammation; nasal polyps; fibroblasts; fibrosis; GROWTH-FACTOR-BETA; SKIN INFLAMMATION; CELLS; PROLIFERATION; EXPRESSION; FEATURES;
D O I：
10.3390/ijms23116308
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页数：9
相关论文
共 29 条
[1]   Oncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation [J].
Boniface, Katia ;
Diveu, Caroline ;
Morel, Franck ;
Pedretti, Nathalie ;
Froger, Josy ;
Ravon, Elisa ;
Garcia, Martine ;
Venereau, Emilie ;
Preisser, Laurence ;
Guignouard, Emmanuel ;
Guillet, Gerard ;
Dagregorio, Guy ;
Pene, Jerome ;
Moles, Jean-Pierre ;
Yssel, Hans ;
Chevalier, Sylvie ;
Bernard, Francois-Xavier ;
Gascan, Hugues ;
Lecron, Jean-Claude .
JOURNAL OF IMMUNOLOGY, 2007, 178 (07) :4615-4622
[2]   IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M [J].
Botelho, Fernando ;
Dubey, Anisha ;
Ayaub, Ehab A. ;
Park, Rex ;
Yip, Ashley ;
Humbles, Allison ;
Kolbeck, Roland ;
Richards, Carl D. .
MEDIATORS OF INFLAMMATION, 2020, 2020
[3]   PPARγ Links BMP2 and TGFβ1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism [J].
Calvier, Laurent ;
Chouvarine, Philippe ;
Legchenko, Ekaterina ;
Hoffmann, Nadine ;
Geldner, Jonas ;
Borchert, Paul ;
Jonigk, Danny ;
Mozes, Miklos M. ;
Hansmann, Georg .
CELL METABOLISM, 2017, 25 (05) :1118-+
[4]   Cytokine Signature and Involvement in Chronic Rhinosinusitis with Nasal Polyps [J].
Carsuzaa, Florent ;
Bequignon, Emilie ;
Dufour, Xavier ;
de Bonnecaze, Guillaume ;
Lecron, Jean-Claude ;
Favot, Laure .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (01)
[5]   Expression of the transforming growth factor β isoforms in inflammatory cells of nasal polyps [J].
Coste, A ;
Lefaucheur, JP ;
Wang, QP ;
Lesprit, E ;
Poron, F ;
Peynegre, R ;
Escudier, E .
ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY, 1998, 124 (12) :1361-1366
[6]   European Position Paper on Rhinosinusitis and Nasal Polyps 2020 [J].
Fokkens, Wytske J. ;
Lund, Valerie J. ;
Hopkins, Claire ;
Hellings, Peter W. ;
Kern, Robert ;
Reitsma, Sietze ;
Toppila-Salmi, Sanna ;
Bernal-Sprekelsen, Manuel ;
Mullol, Joaquim ;
Alobid, Isam ;
Anselmo-Lima, Wilma Terezinha ;
Bachert, Claus ;
Baroody, Fuad ;
von Buchwald, Christian ;
Cervin, Anders ;
Cohen, Noam ;
Constantinidis, Jannis ;
De Gabory, Ludovic ;
Desrosiers, Martin ;
Diamant, Zuzana ;
Douglas, Richard G. ;
Gevaert, Philippe H. ;
Hafner, Anita ;
Harvey, Richard J. ;
Joos, Guy F. ;
Kalogjera, Livije ;
Knill, Andrew ;
Kocks, Janwillem H. ;
Landis, Basile N. ;
Limpens, Jacqueline ;
Lebeer, Sarah ;
Lourenco, Olga ;
Matricardi, Paolo M. ;
Meco, Cem ;
O'Mahony, Liam ;
Philpott, Carl M. ;
Ryan, Dermot ;
Schlosser, Rodney ;
Senior, Brent ;
Smith, Timothy L. ;
Teeling, Thijs ;
Tomazic, Peter Valentin ;
Wang, De Yun ;
Wang, Dehui ;
Zhang, Luo ;
Agius, Adrian M. ;
Ahlstrom-Emanuelsson, Cecilia ;
Alabri, Rashid ;
Albu, Silviu ;
Alhabash, Saied .
RHINOLOGY, 2020, 58 :1-464
[7]   Involvement of IL-1 and Oncostatin M in Acanthosis Associated With Hypertensive Leg Ulcer [J].
Giot, Jean-Philippe ;
Paris, Isabelle ;
Levillain, Pierre ;
Huguier, Vincent ;
Charreau, Sandrine ;
Delwail, Adrianna ;
Garcia, Martine ;
Garnier, Julien ;
Bernard, Francois-Xavier ;
Dagregorio, Guy ;
Guillet, Gerard ;
Morel, Franck ;
Lecron, Jean-Claude ;
Favot, Laure .
AMERICAN JOURNAL OF PATHOLOGY, 2013, 182 (03) :806-818
[8]   Skin Inflammation Induced by the Synergistic Action of IL-17A, IL-22, Oncostatin M, IL-1α, and TNF-α Recapitulates Some Features of Psoriasis [J].
Guilloteau, Karline ;
Paris, Isabelle ;
Pedretti, Nathalie ;
Boniface, Katia ;
Juchaux, Franck ;
Huguier, Vincent ;
Guillet, Gerard ;
Bernard, Francois-Xavier ;
Lecron, Jean-Claude ;
Morel, Franck .
JOURNAL OF IMMUNOLOGY, 2010, 184 (09) :5263-5270
[9]   STAT3 Mediates the Differential Effects of Oncostatin M and TNFα on RA Synovial Fibroblast and Endothelial Cell Function [J].
Hanlon, Megan M. ;
Rakovich, Tatsiana ;
Cunningham, Clare C. ;
Ansboro, Sharon ;
Veale, Douglas J. ;
Fearon, Ursula ;
McGarry, Trudy .
FRONTIERS IN IMMUNOLOGY, 2019, 10
[10]   Histopathological features of nasal polyps with asthma association: An immunohistochemical study [J].
Haruna, S ;
Nakanishi, M ;
Otori, N ;
Moriyama, H .
AMERICAN JOURNAL OF RHINOLOGY, 2004, 18 (03) :165-172
123