| Summary: | 博士 === 國立臺灣大學 === 環境衛生研究所 === 97 === Cigarette smoke (CS) generates reactive oxygen species (ROS) that produces oxidative damage to bronchial epithelial cells. Prolonged repair responses lead to airway remodeling and irreversible airflow limitation. Cigarette smoke may cause bronchial epithelium damage and orchestrate airway remodeling resulting from activation of epithelial repair and mediator release. Thioredoxin (TRX) has anti-oxidation capability against oxidative stress, and involves in cell growth and differentiation. The aim of this study was to investigate how TRX mediates CS-induced oxidative damage and modulated any onset/progression of airway remodeling and its downstream mitogen-activated protein kinase (MAPK) in human airway epithelial cells.
Normal human epithelial cells (BEAS-2B) and thioredoxin over-expressing cells were used for various experiments including different doses and periods of CS exposure. Results of this study showed that high-dose CS extract stimulated ROS generation and decreased TRX expression resulting in apoptosis of BEAS-2B cells. Otherwise, BEAS-2B cells exposure to low-dose CS increased TRX expression. Additionally, CS exposure interfered with gene expression of remodeling factors such as activation of the transforming growth factor (TGF)-β1, epidermal growth factor receptor (EGFR) and cyclin-dependent kinase inhibitor (p21), but attenuated of matrix metalloproteinases (MMP)-9.
BEAS-2B cells over-expressing TRX suppressed CS-induced apoptosis through reduction of ROS generation, inactivation of apoptosis signal regulating kinase (ASK)-1, and attenuation of p38 and c-Jun N-terminal kinase (JNK). After being neutralized with anti-TGF-β1 antibody, TRX over-expressing cells exposed CS decreased gene expression of MMP-9, EGFR and p21. It suggests that TGF-β1 regulated TRX expression may further prevent the underlying CS-induced airway remodeling through MAPK activation and MMP-9 augmentation. This study demonstrated that the transfected TRX gene had redox capacity to reduce CS-induced oxidative damage. The mediating mechanism of TRX against CS-induced damage can be applied in further preventive and therapeutic studies.
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