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Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation

Commensal microbes cross talk with their colonized mucosa. We show that microbes and their cell wall components induce an inflammatory response in cultured human mucosal cells derived from the nonmalignant nasopharyngeal epithelium (NNE) cells in vitro. NNE cells show significant induction of NF-κB...

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Autores principales: Zhou, Xiaoying, Matskova, Liudmila, Zheng, Shixing, Wang, Xiaoxia, Wang, Yifang, Xiao, Xue, Mo, Yingxi, Wölke, Marleen, Li, Limei, Zheng, Qian, Huang, Guangwu, Zhang, Zhe, Ernberg, Ingemar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353648/
https://www.ncbi.nlm.nih.gov/pubmed/35938161
http://dx.doi.org/10.3389/fcell.2022.861916
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author Zhou, Xiaoying
Matskova, Liudmila
Zheng, Shixing
Wang, Xiaoxia
Wang, Yifang
Xiao, Xue
Mo, Yingxi
Wölke, Marleen
Li, Limei
Zheng, Qian
Huang, Guangwu
Zhang, Zhe
Ernberg, Ingemar
author_facet Zhou, Xiaoying
Matskova, Liudmila
Zheng, Shixing
Wang, Xiaoxia
Wang, Yifang
Xiao, Xue
Mo, Yingxi
Wölke, Marleen
Li, Limei
Zheng, Qian
Huang, Guangwu
Zhang, Zhe
Ernberg, Ingemar
author_sort Zhou, Xiaoying
collection PubMed
description Commensal microbes cross talk with their colonized mucosa. We show that microbes and their cell wall components induce an inflammatory response in cultured human mucosal cells derived from the nonmalignant nasopharyngeal epithelium (NNE) cells in vitro. NNE cells show significant induction of NF-κB with nuclear shuttling and inflammatory gene response when exposed to Gram-positive bacteria (streptococci) or peptidoglycan (PGN), a component of the Gram-positive bacterial cell wall. This response is abrogated in nasopharyngeal carcinoma (NPC)–derived cell lines. The inflammatory response induced by NF-κB signaling was blocked at two levels in the tumor-derived cells. We found that NF-κB was largely trapped in lipid droplets (LDs) in the cytoplasm of the NPC-derived cells, while the increased expression of lysine-specific histone demethylase 1 (LSD1, a repressive nuclear factor) reduces the response mediated by remaining NF-κB at the promoters responding to inflammatory stimuli. This refractory response in NPC cells might be a consequence of long-term exposure to microbes in vivo during carcinogenic progression. It may contribute to the decreased antitumor immune responses in NPC, among others despite heavy T-helper cell infiltration, and thus facilitate tumor progression.
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spelling pubmed-93536482022-08-06 Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation Zhou, Xiaoying Matskova, Liudmila Zheng, Shixing Wang, Xiaoxia Wang, Yifang Xiao, Xue Mo, Yingxi Wölke, Marleen Li, Limei Zheng, Qian Huang, Guangwu Zhang, Zhe Ernberg, Ingemar Front Cell Dev Biol Cell and Developmental Biology Commensal microbes cross talk with their colonized mucosa. We show that microbes and their cell wall components induce an inflammatory response in cultured human mucosal cells derived from the nonmalignant nasopharyngeal epithelium (NNE) cells in vitro. NNE cells show significant induction of NF-κB with nuclear shuttling and inflammatory gene response when exposed to Gram-positive bacteria (streptococci) or peptidoglycan (PGN), a component of the Gram-positive bacterial cell wall. This response is abrogated in nasopharyngeal carcinoma (NPC)–derived cell lines. The inflammatory response induced by NF-κB signaling was blocked at two levels in the tumor-derived cells. We found that NF-κB was largely trapped in lipid droplets (LDs) in the cytoplasm of the NPC-derived cells, while the increased expression of lysine-specific histone demethylase 1 (LSD1, a repressive nuclear factor) reduces the response mediated by remaining NF-κB at the promoters responding to inflammatory stimuli. This refractory response in NPC cells might be a consequence of long-term exposure to microbes in vivo during carcinogenic progression. It may contribute to the decreased antitumor immune responses in NPC, among others despite heavy T-helper cell infiltration, and thus facilitate tumor progression. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9353648/ /pubmed/35938161 http://dx.doi.org/10.3389/fcell.2022.861916 Text en Copyright © 2022 Zhou, Matskova, Zheng, Wang, Wang, Xiao, Mo, Wölke, Li, Zheng, Huang, Zhang and Ernberg. 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 Cell and Developmental Biology
Zhou, Xiaoying
Matskova, Liudmila
Zheng, Shixing
Wang, Xiaoxia
Wang, Yifang
Xiao, Xue
Mo, Yingxi
Wölke, Marleen
Li, Limei
Zheng, Qian
Huang, Guangwu
Zhang, Zhe
Ernberg, Ingemar
Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation
title Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation
title_full Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation
title_fullStr Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation
title_full_unstemmed Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation
title_short Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation
title_sort mechanisms of anergic inflammatory response in nasopharyngeal carcinoma cells despite ubiquitous constitutive nf-κb activation
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353648/
https://www.ncbi.nlm.nih.gov/pubmed/35938161
http://dx.doi.org/10.3389/fcell.2022.861916
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