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(Chest. 2006;129:1298-1304.)
© 2006 American College of Chest Physicians

High-Level Expression of Matrix-Associated Transforming Growth Factor-ß1 in Benign Airway Stenosis*

Christian Karagiannidis, MD; Viorica Velehorschi; Barbara Obertrifter; Hans-Nicol Macha, MD; Albert Linder, MD and Lutz Freitag, MD, FCCP

* From the Lungenklinik Hemer, Center for Pulmonary Medicine and Thoracic Surgery, Hemer, Germany.

Correspondence to: Lutz Freitag, MD, FCCP, Lungenklinik Hemer, Center for Pulmonary Medicine and Thoracic Surgery, Theo-Funccius Str 1, 58675 Hemer, Germany; e-mail: freitag-hemer{at}t-online.de

Abstract

Study objectives: Acquired tracheal and subglottic stenosis frequently leads to severe airway narrowing, which requires repeated interventions, such as dilatation, laser resection, stent implantation, or surgery. To get a more detailed insight into the pathogenesis of this condition, we investigated the expression of profibrotic cytokines and the proliferation of the airway wall in benign human airway stenoses.

Methods: Specimens from patients with subglottic and tracheal stenosis and stent-related stenoses were obtained (n = 20) for reverse transcription (RT) polymerase chain reaction (PCR) analysis and immunohistochemistry testing.

Results: Transforming growth factor (TGF)-ß1 messenger RNA expression was significantly increased in biopsy specimens from stent-related stenoses compared to nonstenotic control sections. In contrast, TGF-ß3 and interleukin-1ß showed no such differences in messenger RNA expression. Immunohistochemistry revealed a strong matrix-associated, subepithelial expression of TGF-ß1 in tracheal stenosis. Proliferating Ki-67-positive cells were mainly localized in the basal epithelial layer. Only 2 of 16 patients with tracheal stenoses and 3 of 4 patients with stent-related stenoses showed a weak expression of Ki-67-positive cells in the subepithelium. Furthermore, TGF-ß1 dose-dependently enhanced the proliferation of human lung fibroblasts in vitro, even in the presence of mitomycin-C.

Conclusion: While a weak subepithelial proliferation occurs in stent-related stenoses, the dominant factor in late stages of untreated tracheal stenoses seems to be the high-level expression of TGF-ß1 and the deposition of extracellular matrix.

Key Words: Ki-67 • proliferation • stent • tracheal stenosis • transforming growth factor-ß






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