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PD-L1 Up-Regulation in Prostate Cancer Cells by Porphyromonas gingivalis

Chronic inflammation is known to contribute to various human cancers. Porphyromonas gingivalis (P. gingivalis), is a gram-negative oral keystone pathogen that may cause severe periodontitis and expresses several virulence factors to affect the host immune system. Periodontitis is a chronic infectiou...

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Autores principales: Groeger, Sabine, Wu, Fan, Wagenlehner, Florian, Dansranjav, Temuujin, Ruf, Sabine, Denter, Fabian, Meyle, Joerg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277116/
https://www.ncbi.nlm.nih.gov/pubmed/35846769
http://dx.doi.org/10.3389/fcimb.2022.935806
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author Groeger, Sabine
Wu, Fan
Wagenlehner, Florian
Dansranjav, Temuujin
Ruf, Sabine
Denter, Fabian
Meyle, Joerg
author_facet Groeger, Sabine
Wu, Fan
Wagenlehner, Florian
Dansranjav, Temuujin
Ruf, Sabine
Denter, Fabian
Meyle, Joerg
author_sort Groeger, Sabine
collection PubMed
description Chronic inflammation is known to contribute to various human cancers. Porphyromonas gingivalis (P. gingivalis), is a gram-negative oral keystone pathogen that may cause severe periodontitis and expresses several virulence factors to affect the host immune system. Periodontitis is a chronic infectious disease that while progression, may cause loss of attachment and destruction of the tooth supporting tissues. Prostate cancer is one of the most common malignancies in men. Increasing evidence links periodontitis with prostate cancer, however the mechanisms explaining this relationship remain unclear. The aim of this study was to investigate the expression and signaling pathway of programmed death ligand 1 (PD-L1) in a prostate cancer cell line after infection with P. gingivalis and stimulation with P. gingivalis components to reveal the mechanism of tumor-induced immune evasion associated with bacterial infection in the tumor environment. Prostate cancer cells were infected with different concentrations of viable P. gingivalis and treated with different concentrations of heat-killed P. gingivalis and P. gingivalis cell components, including the total membrane fraction, inner membrane fraction, outer membrane fraction, cytosolic fraction and peptidoglycan (PGN). Chemical inhibitors were used to block different important molecules of signaling pathways to assess the participating signal transduction mechanisms. PD-L1 expression was detected by Western blot after 24 h of infection. PD-L1 was demonstrated to be upregulated in prostate cancer cells after infection with viable and with heat-killed P. gingivalis membrane fractions. Also isolated PGN induced PD-L1 up-regulation. The upregulation was mediated by the NOD1/NOD2 signaling pathway. No upregulation could be detected after treatment of the cells with P. gingivalis lipopolysaccharide (LPS). These results indicate, that chronic inflammatory disease can contribute to tumor immune evasion by modifying the tumor microenvironment. Thus, chronic infection possibly plays an essential role in the immune response and may promote the development and progression of prostate cancer.
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spelling pubmed-92771162022-07-14 PD-L1 Up-Regulation in Prostate Cancer Cells by Porphyromonas gingivalis Groeger, Sabine Wu, Fan Wagenlehner, Florian Dansranjav, Temuujin Ruf, Sabine Denter, Fabian Meyle, Joerg Front Cell Infect Microbiol Cellular and Infection Microbiology Chronic inflammation is known to contribute to various human cancers. Porphyromonas gingivalis (P. gingivalis), is a gram-negative oral keystone pathogen that may cause severe periodontitis and expresses several virulence factors to affect the host immune system. Periodontitis is a chronic infectious disease that while progression, may cause loss of attachment and destruction of the tooth supporting tissues. Prostate cancer is one of the most common malignancies in men. Increasing evidence links periodontitis with prostate cancer, however the mechanisms explaining this relationship remain unclear. The aim of this study was to investigate the expression and signaling pathway of programmed death ligand 1 (PD-L1) in a prostate cancer cell line after infection with P. gingivalis and stimulation with P. gingivalis components to reveal the mechanism of tumor-induced immune evasion associated with bacterial infection in the tumor environment. Prostate cancer cells were infected with different concentrations of viable P. gingivalis and treated with different concentrations of heat-killed P. gingivalis and P. gingivalis cell components, including the total membrane fraction, inner membrane fraction, outer membrane fraction, cytosolic fraction and peptidoglycan (PGN). Chemical inhibitors were used to block different important molecules of signaling pathways to assess the participating signal transduction mechanisms. PD-L1 expression was detected by Western blot after 24 h of infection. PD-L1 was demonstrated to be upregulated in prostate cancer cells after infection with viable and with heat-killed P. gingivalis membrane fractions. Also isolated PGN induced PD-L1 up-regulation. The upregulation was mediated by the NOD1/NOD2 signaling pathway. No upregulation could be detected after treatment of the cells with P. gingivalis lipopolysaccharide (LPS). These results indicate, that chronic inflammatory disease can contribute to tumor immune evasion by modifying the tumor microenvironment. Thus, chronic infection possibly plays an essential role in the immune response and may promote the development and progression of prostate cancer. Frontiers Media S.A. 2022-06-29 /pmc/articles/PMC9277116/ /pubmed/35846769 http://dx.doi.org/10.3389/fcimb.2022.935806 Text en Copyright © 2022 Groeger, Wu, Wagenlehner, Dansranjav, Ruf, Denter and Meyle 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 Cellular and Infection Microbiology
Groeger, Sabine
Wu, Fan
Wagenlehner, Florian
Dansranjav, Temuujin
Ruf, Sabine
Denter, Fabian
Meyle, Joerg
PD-L1 Up-Regulation in Prostate Cancer Cells by Porphyromonas gingivalis
title PD-L1 Up-Regulation in Prostate Cancer Cells by Porphyromonas gingivalis
title_full PD-L1 Up-Regulation in Prostate Cancer Cells by Porphyromonas gingivalis
title_fullStr PD-L1 Up-Regulation in Prostate Cancer Cells by Porphyromonas gingivalis
title_full_unstemmed PD-L1 Up-Regulation in Prostate Cancer Cells by Porphyromonas gingivalis
title_short PD-L1 Up-Regulation in Prostate Cancer Cells by Porphyromonas gingivalis
title_sort pd-l1 up-regulation in prostate cancer cells by porphyromonas gingivalis
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277116/
https://www.ncbi.nlm.nih.gov/pubmed/35846769
http://dx.doi.org/10.3389/fcimb.2022.935806
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