Combination Of Tweak And Tgf-Beta 1 Induces The Production Of Tslp, Rantes, And Tarc In Beas-2b Human Bronchial Epithelial Cells During Epithelial-Mesenchymal Transition
EXPERIMENTAL LUNG RESEARCH(2018)
Abstract
Aim of the study: In patients with asthma, chronic inflammatory processes and the subsequent remodeling of the airways contribute to the symptoms and the pathophysiological changes. Epithelial-mesenchymal transition (EMT) is thought to play an important role in tissue remodeling. Previous reports show that tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a cytokine of the TNF superfamily, exerts pro-inflammatory effects, and enhances transforming growth factor (TGF)-beta-induced EMT in bronchial epithelial cells. In this study, we investigated the TWEAK-induced cytokine and chemokine production in the human bronchial epithelial cell line BEAS-2B during EMT. Materials and Methods: Quantitative real-time RT-PCR, enzyme-linked immunosorbent assays, western blotting, and immunohistochemistry were used to define the production of cytokines and chemokines. Results: We found that TWEAK increases mRNA and protein levels of thymic stromal lymphopoietin (TSLP), monocyte chemoattractant protein -1 (MCP-1), regulated upon activation normal T cell express sequence (RANTES), and IL-8 in BEAS-2B bronchial epithelial cells. Moreover, co-treatment with TWEAK and TGF-beta 1 induces not only features of EMT but also enhances the production of TSLP and RANTES. Thymus- and activation-regulated chemokines (TARC) production is induced by the co-treatment of TWEAK and TGF-beta 1 but not by TWEAK or TGF-beta 1 stimulation alone. Furthermore, the increased mRNA expression of TSLP and RANTES after co-treatment with TWEAK and TGF-beta 1 is prevented by inhibitors of Smad-independent signaling pathways. Conclusions: In the present study, we have revealed a novel mechanism for the production of asthma-related cytokines and chemokines in EMT driven by the co-stimulation with TWEAK and TGF-beta 1. We conclude that cellular EMT processes caused by TWEAK and TGF-beta 1 may contribute to chronic airway inflammation and remodeling.
MoreTranslated text
Key words
Bronchial epithelial cells, epithelial-mesenchymal transition, RANTES, TARC, TGF-beta, TSLP, TWEAK
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined