- 作者：Nicholas Van Bruaene ; Lara Derycke ; Claudina Angela Perez-Novo ; Philippe Gevaert ; Gabriele Holtappels ; Natalie De Ruyck ; Claude Cuvelier ; Paul Van Cauwenberge ; Claus Bachert
- 关键词：Chronic rhinosinusitis ; collagen ; inflammation ; nasal polyposis ; phospho-Smad 2 ; remodeling ; TGF-β
- 刊名：Journal of Allergy and Clinical Immunology
- 出版年：2009
- 出版时间：August 2009
- 年：2009
- 卷：124
- 期：2
- 页码：253-259.e2
- 全文大小：548 K
Background
Chronic rhinosinusitis is an inflammatory disease with distinct cytokine and remodeling patterns.Objective
The objective was to analyze the presence of TGF-β isoforms, receptors, intracellular signaling, and collagen deposition in chronic rhinosinusitis.
Methods
Sinonasal mucosal samples obtained from chronic rhinosinusitis with nasal polyps (CRSwNP; n = 13), chronic rhinosinusitis without nasal polyps (CRSsNP; n = 13), and controls (n = 10) were analyzed for TGF-β isoforms 1 and 2 by means of ELISA and IHC, and for TGF-β R1, 2, and 3 by RT-PCR and IHC. As downstream proteins, phospho-Smad 2 (pSmad 2) and collagen were analyzed by performing immunostaining and picrosirius red staining, respectively.
Results
TGF-β 1 and 2 protein concentrations, TGF-β receptor (R) I and TGF-β RIII mRNA expression, the number of pSmad 2–positive cells, and total collagen amount were significantly higher in CRSsNP versus controls. In CRSwNP, TGF-β 1 protein concentration, TGF-β RII and TGF-β RIII mRNA expression, the number of pSmad 2–positive cells, and total collagen amount were significantly lower versus controls. Only TGF-β 2 protein was found higher in CRSwNP versus controls.
Conclusion
A high TGF-β 1 protein expression, increased TGF-β RI expression, and a high number of pSmad 2–positive cells all indicate an enhanced TGF-β signaling in CRSsNP, whereas a low TGF-β 1 protein concentration, a decreased expression of TGF-β RII, and a low number of pSmad 2–positive cells in CRSwNP indicate a low level of TGF-β signaling in CRSwNP. These findings are compatible with the remodeling patterns observed, reflected by a lack of collagen in CRSwNP, and excessive collagen production with thickening of the collagen fibers in the extracellular matrix in CRSsNP.