PMID- 30676129 OWN - NLM STAT- MEDLINE DCOM- 20190715 LR - 20221207 IS - 1521-0499 (Electronic) IS - 0190-2148 (Linking) VI - 44 IP - 7 DP - 2018 Sep TI - Combination of TWEAK and TGF-beta1 induces the production of TSLP, RANTES, and TARC in BEAS-2B human bronchial epithelial cells during epithelial-mesenchymal transition. PG - 332-343 LID - 10.1080/01902148.2018.1522558 [doi] AB - 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-beta1 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-beta1 but not by TWEAK or TGF-beta1 stimulation alone. Furthermore, the increased mRNA expression of TSLP and RANTES after co-treatment with TWEAK and TGF-beta1 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-beta1. We conclude that cellular EMT processes caused by TWEAK and TGF-beta1 may contribute to chronic airway inflammation and remodeling. FAU - Matsuno, Kei AU - Matsuno K AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. AD - b Research Institute for Diseases of Old Ages, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Harada, Norihiro AU - Harada N AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. AD - b Research Institute for Diseases of Old Ages, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. AD - c Atopy (Allergy) Research Center, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Harada, Sonoko AU - Harada S AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. AD - b Research Institute for Diseases of Old Ages, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. AD - c Atopy (Allergy) Research Center, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Takeshige, Tomohito AU - Takeshige T AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. AD - b Research Institute for Diseases of Old Ages, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Ishimori, Ayako AU - Ishimori A AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Itoigawa, Yukinari AU - Itoigawa Y AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Katsura, Yoko AU - Katsura Y AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Kodama, Yuzo AU - Kodama Y AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. AD - b Research Institute for Diseases of Old Ages, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Makino, Fumihiko AU - Makino F AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Ito, Jun AU - Ito J AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. AD - b Research Institute for Diseases of Old Ages, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Atsuta, Ryo AU - Atsuta R AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Akiba, Hisaya AU - Akiba H AD - d Department of Immunology, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. FAU - Takahashi, Kazuhisa AU - Takahashi K AD - a Department of Respiratory Medicine, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. AD - b Research Institute for Diseases of Old Ages, Faculty of Medicine , Graduate School of Medicine, Juntendo University , Tokyo , Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190124 PL - England TA - Exp Lung Res JT - Experimental lung research JID - 8004944 RN - 0 (CCL17 protein, human) RN - 0 (Chemokine CCL17) RN - 0 (Chemokine CCL5) RN - 0 (Cytokine TWEAK) RN - 0 (Cytokines) RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta1) RN - GT0IL38SP4 (Thymic Stromal Lymphopoietin) SB - IM MH - Airway Remodeling MH - Asthma/metabolism MH - Bronchi/cytology MH - Cell Line MH - Chemokine CCL17/*biosynthesis MH - Chemokine CCL5/*biosynthesis MH - Cytokine TWEAK/*pharmacology MH - Cytokines/*biosynthesis MH - Epithelial Cells/*metabolism MH - *Epithelial-Mesenchymal Transition MH - Humans MH - Transforming Growth Factor beta1/*pharmacology MH - Thymic Stromal Lymphopoietin OTO - NOTNLM OT - Bronchial epithelial cells OT - RANTES OT - TARC OT - TGF-beta OT - TSLP OT - TWEAK OT - epithelial-mesenchymal transition EDAT- 2019/01/25 06:00 MHDA- 2019/07/16 06:00 CRDT- 2019/01/25 06:00 PHST- 2019/01/25 06:00 [pubmed] PHST- 2019/07/16 06:00 [medline] PHST- 2019/01/25 06:00 [entrez] AID - 10.1080/01902148.2018.1522558 [doi] PST - ppublish SO - Exp Lung Res. 2018 Sep;44(7):332-343. doi: 10.1080/01902148.2018.1522558. Epub 2019 Jan 24.