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A20 undermines alternative NF-κB activity and expression of anti-apoptotic genes in Helicobacter pylori infection

A hallmark of infection by the pathogen Helicobacter pylori, which colonizes the human gastric epithelium, is the simultaneous activation of the classical and alternative nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, underlying inflammation and cell survival. Here,...

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Autores principales: Lim, Michelle C. C., Maubach, Gunter, Birkl-Toeglhofer, Anna M., Haybaeck, Johannes, Vieth, Michael, Naumann, Mchael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799570/
https://www.ncbi.nlm.nih.gov/pubmed/35089437
http://dx.doi.org/10.1007/s00018-022-04139-y
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author Lim, Michelle C. C.
Maubach, Gunter
Birkl-Toeglhofer, Anna M.
Haybaeck, Johannes
Vieth, Michael
Naumann, Mchael
author_facet Lim, Michelle C. C.
Maubach, Gunter
Birkl-Toeglhofer, Anna M.
Haybaeck, Johannes
Vieth, Michael
Naumann, Mchael
author_sort Lim, Michelle C. C.
collection PubMed
description A hallmark of infection by the pathogen Helicobacter pylori, which colonizes the human gastric epithelium, is the simultaneous activation of the classical and alternative nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, underlying inflammation and cell survival. Here, we report that the classical NF-κB target gene product A20 contributes to the negative regulation of alternative NF-κB signaling in gastric epithelial cells infected by H. pylori. Mechanistically, the de novo synthesized A20 protein interacts with tumor necrosis factor receptor-associated factor-interacting protein with forkhead-associated domain (TIFA) and thereby interferes with the association of TIFA with the NIK regulatory complex. We also show that alternative NF-κB activity contributes to the up-regulation of anti-apoptotic genes, such as baculoviral IAP repeat containing 2 (BIRC2), BIRC3 and B-cell lymphoma 2-related protein A1 (BCL2A1) in gastric epithelial cells. Furthermore, the observed over-expression of RelB in human gastric biopsies with type B gastritis and RelB-dependent suppression of apoptotic cell death emphasize an important role of the alternative NF-κB pathway in H. pylori infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04139-y.
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spelling pubmed-87995702022-02-02 A20 undermines alternative NF-κB activity and expression of anti-apoptotic genes in Helicobacter pylori infection Lim, Michelle C. C. Maubach, Gunter Birkl-Toeglhofer, Anna M. Haybaeck, Johannes Vieth, Michael Naumann, Mchael Cell Mol Life Sci Original Article A hallmark of infection by the pathogen Helicobacter pylori, which colonizes the human gastric epithelium, is the simultaneous activation of the classical and alternative nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, underlying inflammation and cell survival. Here, we report that the classical NF-κB target gene product A20 contributes to the negative regulation of alternative NF-κB signaling in gastric epithelial cells infected by H. pylori. Mechanistically, the de novo synthesized A20 protein interacts with tumor necrosis factor receptor-associated factor-interacting protein with forkhead-associated domain (TIFA) and thereby interferes with the association of TIFA with the NIK regulatory complex. We also show that alternative NF-κB activity contributes to the up-regulation of anti-apoptotic genes, such as baculoviral IAP repeat containing 2 (BIRC2), BIRC3 and B-cell lymphoma 2-related protein A1 (BCL2A1) in gastric epithelial cells. Furthermore, the observed over-expression of RelB in human gastric biopsies with type B gastritis and RelB-dependent suppression of apoptotic cell death emphasize an important role of the alternative NF-κB pathway in H. pylori infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04139-y. Springer International Publishing 2022-01-28 2022 /pmc/articles/PMC8799570/ /pubmed/35089437 http://dx.doi.org/10.1007/s00018-022-04139-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Lim, Michelle C. C.
Maubach, Gunter
Birkl-Toeglhofer, Anna M.
Haybaeck, Johannes
Vieth, Michael
Naumann, Mchael
A20 undermines alternative NF-κB activity and expression of anti-apoptotic genes in Helicobacter pylori infection
title A20 undermines alternative NF-κB activity and expression of anti-apoptotic genes in Helicobacter pylori infection
title_full A20 undermines alternative NF-κB activity and expression of anti-apoptotic genes in Helicobacter pylori infection
title_fullStr A20 undermines alternative NF-κB activity and expression of anti-apoptotic genes in Helicobacter pylori infection
title_full_unstemmed A20 undermines alternative NF-κB activity and expression of anti-apoptotic genes in Helicobacter pylori infection
title_short A20 undermines alternative NF-κB activity and expression of anti-apoptotic genes in Helicobacter pylori infection
title_sort a20 undermines alternative nf-κb activity and expression of anti-apoptotic genes in helicobacter pylori infection
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799570/
https://www.ncbi.nlm.nih.gov/pubmed/35089437
http://dx.doi.org/10.1007/s00018-022-04139-y
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