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Combination of TWEAK and TGF-β1 Induces the Production of TSLP, RANTES, and TARC in BEAS-2B Human Bronchial Epithelial Cells During Epithelial-Mesenchymal Transition

Combination of TWEAK and TGF-β1 Induces the Production of TSLP, RANTES, and TARC in BEAS-2B Human Bronchial Epithelial Cells During Epithelial-Mesenchymal Transition

Kei Matsuno, Norihiro Harada, Sonoko Harada, Tomohito Takeshige, Ayako Ishimori, Yukinari Itoigawa, Yoko Katsura, Yuzo Kodama, Fumihiko Makino, Jun Ito, Ryo Atsuta, Hisaya Akiba, Kazuhisa Takahashi

Exp Lung Res. 2018 Sep;44(7):332-343.

PMID: 30676129

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)-β-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-β1 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-β1 but not by TWEAK or TGF-β1 stimulation alone. Furthermore, the increased mRNA expression of TSLP and RANTES after co-treatment with TWEAK and TGF-β1 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-β1. We conclude that cellular EMT processes caused by TWEAK and TGF-β1 may contribute to chronic airway inflammation and remodeling.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413139	RANTES human			Price
IAR42413142	TARC human			Price

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