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Profibrotic transforming growth factor beta 1 and activin A are increased in nasal polyp tissue and induced in nasal polyp epithelium by cigarette smoke and Toll-like receptor 3 ligation.
- Source :
-
International forum of allergy & rhinology [Int Forum Allergy Rhinol] 2015 Jul; Vol. 5 (7), pp. 573-82. Date of Electronic Publication: 2015 Apr 25. - Publication Year :
- 2015
-
Abstract
- Background: The mechanism of airway remodeling in chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unknown. We wished to determine whether profibrotic transforming growth factor beta 1 (TGF-β1) and activin A and their downstream signaling proteins are increased in CRSwNP and if they are regulated in epithelial cells by noxious or inflammatory stimuli.<br />Methods: Frozen tissue from CRSwNP patients, healthy control (HC) middle turbinates, and sinus tissue from CRS without NP (CRSsNP) patients were immunostained for TGF-β1, activin A, and downstream signaling proteins. Primary nasal epithelial cells (PNECs) from HCs and CRSwNP patients were cultured in media, cigarette smoke extract (CSE), or double-stranded RNA (dsRNA) (a ligand for Toll-like receptor-3) and examined for inflammatory and profibrotic genes using real-time polymerase chain reaction (PCR).<br />Results: CRSwNP patients showed increased TGF-β1 and activin A in the stroma, increased TGF-β1 signaling (phosphorylated Smad2/3) in the stroma and epithelium, and increased Smad3-dependent Snail1 in the stroma. Immunostaining for TGF-β1, pSmad2/3, and Snail1 in CRSwNP patients was highly correlated. Immunostaining for pSmad2/3 and Snail1 was similar in CRSwNP and CRSsNP patients. Compared to HCs, PNECs from CRSwNP patients were more responsive to CSE and dsRNA in terms of TGF-β1 and activin A and more strongly induced by dsRNA in terms of chemokines.<br />Conclusion: Increased TGF-β1 and activin A and increased downstream TGF-β1 signaling is present in CRSwNP patients, primarily in the stroma. This may contribute to features of airway remodeling previously described. PNECs from CRSwNP patients are induced to produce TGF-β1 and activin A by CSE and dsRNA, suggesting that cigarette smoke and viral infection might also contribute to airway remodeling.<br /> (© 2015 ARS-AAOA, LLC.)
- Subjects :
- Adult
Aged
Biopsy
Chronic Disease
Female
Humans
Male
Middle Aged
Nasal Mucosa metabolism
Nasal Polyps pathology
Paranasal Sinuses pathology
Real-Time Polymerase Chain Reaction
Rhinitis pathology
Sinusitis pathology
Turbinates pathology
Young Adult
Activins metabolism
Airway Remodeling physiology
Nasal Mucosa drug effects
Nasal Polyps metabolism
Rhinitis metabolism
Sinusitis metabolism
Smoking adverse effects
Toll-Like Receptor 3 metabolism
Transforming Growth Factor beta1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2042-6984
- Volume :
- 5
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- International forum of allergy & rhinology
- Publication Type :
- Academic Journal
- Accession number :
- 25914020
- Full Text :
- https://doi.org/10.1002/alr.21516