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TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma

Tumor necrosis factor (TNF)-like cytokine 1A (TL1A), a member of the TNF family, exists in the form of membrane-bound (mTL1A) and soluble protein (sTL1A). TL1A binding its only known functional receptor death domain receptor 3 (DR3) affects the transmission of various signals. This study first propo...

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Autores principales: Zhang, Dong, Yang, Hui, Dong, Xue-Li, Zhang, Jin-Tao, Liu, Xiao-Fei, Pan, Yun, Zhang, Jian, Xu, Jia-Wei, Wang, Zi-Han, Cui, Wen-Jing, Dong, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8963920/
https://www.ncbi.nlm.nih.gov/pubmed/35359966
http://dx.doi.org/10.3389/fimmu.2022.854995
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author Zhang, Dong
Yang, Hui
Dong, Xue-Li
Zhang, Jin-Tao
Liu, Xiao-Fei
Pan, Yun
Zhang, Jian
Xu, Jia-Wei
Wang, Zi-Han
Cui, Wen-Jing
Dong, Liang
author_facet Zhang, Dong
Yang, Hui
Dong, Xue-Li
Zhang, Jin-Tao
Liu, Xiao-Fei
Pan, Yun
Zhang, Jian
Xu, Jia-Wei
Wang, Zi-Han
Cui, Wen-Jing
Dong, Liang
author_sort Zhang, Dong
collection PubMed
description Tumor necrosis factor (TNF)-like cytokine 1A (TL1A), a member of the TNF family, exists in the form of membrane-bound (mTL1A) and soluble protein (sTL1A). TL1A binding its only known functional receptor death domain receptor 3 (DR3) affects the transmission of various signals. This study first proposed that the TL1A/DR3 axis was significantly upregulated in patients and mice with both asthma and high TNF-a expression and in TNF-a-stimulated epithelial Beas-2B cells. Two independent approaches were used to demonstrate that the TL1A/DR3 axis of mice was strongly correlated with TNF-a in terms of exacerbating asthmatic epithelial–mesenchymal transformation (EMT). First, high expression levels of EMT proteins (e.g., collagen I, fibronectin, N-cadherin, and vimentin) and TL1A/DR3 axis were observed when mice airways were stimulated by recombinant mouse TNF-a protein. Moreover, EMT protein and TL1A/DR3 axis expression synchronously decreased after mice with OVA-induced asthma were treated with infliximab by neutralizing TNF-a activity. Furthermore, the OVA-induced EMT of asthmatic mice was remarkably improved upon the deletion of the TL1A/DR3 axis by knocking out the TL1A gene. TL1A siRNA remarkably intervened EMT formation induced by TNF-a in the Beas-2B cells. In addition, EMT was induced by the addition of high concentrations of recombinant human sTL1A with the cell medium. The TL1A overexpression via pc-mTL1A in vitro remarkably increased the EMT formation induced by TNF-a. Overall, these findings indicate that the TL1A/DR3 axis may have a therapeutic role for asthmatic with high TNF-a level.
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spelling pubmed-89639202022-03-30 TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma Zhang, Dong Yang, Hui Dong, Xue-Li Zhang, Jin-Tao Liu, Xiao-Fei Pan, Yun Zhang, Jian Xu, Jia-Wei Wang, Zi-Han Cui, Wen-Jing Dong, Liang Front Immunol Immunology Tumor necrosis factor (TNF)-like cytokine 1A (TL1A), a member of the TNF family, exists in the form of membrane-bound (mTL1A) and soluble protein (sTL1A). TL1A binding its only known functional receptor death domain receptor 3 (DR3) affects the transmission of various signals. This study first proposed that the TL1A/DR3 axis was significantly upregulated in patients and mice with both asthma and high TNF-a expression and in TNF-a-stimulated epithelial Beas-2B cells. Two independent approaches were used to demonstrate that the TL1A/DR3 axis of mice was strongly correlated with TNF-a in terms of exacerbating asthmatic epithelial–mesenchymal transformation (EMT). First, high expression levels of EMT proteins (e.g., collagen I, fibronectin, N-cadherin, and vimentin) and TL1A/DR3 axis were observed when mice airways were stimulated by recombinant mouse TNF-a protein. Moreover, EMT protein and TL1A/DR3 axis expression synchronously decreased after mice with OVA-induced asthma were treated with infliximab by neutralizing TNF-a activity. Furthermore, the OVA-induced EMT of asthmatic mice was remarkably improved upon the deletion of the TL1A/DR3 axis by knocking out the TL1A gene. TL1A siRNA remarkably intervened EMT formation induced by TNF-a in the Beas-2B cells. In addition, EMT was induced by the addition of high concentrations of recombinant human sTL1A with the cell medium. The TL1A overexpression via pc-mTL1A in vitro remarkably increased the EMT formation induced by TNF-a. Overall, these findings indicate that the TL1A/DR3 axis may have a therapeutic role for asthmatic with high TNF-a level. Frontiers Media S.A. 2022-03-14 /pmc/articles/PMC8963920/ /pubmed/35359966 http://dx.doi.org/10.3389/fimmu.2022.854995 Text en Copyright © 2022 Zhang, Yang, Dong, Zhang, Liu, Pan, Zhang, Xu, Wang, Cui and Dong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhang, Dong
Yang, Hui
Dong, Xue-Li
Zhang, Jin-Tao
Liu, Xiao-Fei
Pan, Yun
Zhang, Jian
Xu, Jia-Wei
Wang, Zi-Han
Cui, Wen-Jing
Dong, Liang
TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma
title TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma
title_full TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma
title_fullStr TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma
title_full_unstemmed TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma
title_short TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma
title_sort tl1a/dr3 axis, a key target of tnf-a, augments the epithelial–mesenchymal transformation of epithelial cells in ova-induced asthma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8963920/
https://www.ncbi.nlm.nih.gov/pubmed/35359966
http://dx.doi.org/10.3389/fimmu.2022.854995
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