Cargando…
Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells
Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood–brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086651/ https://www.ncbi.nlm.nih.gov/pubmed/27754355 http://dx.doi.org/10.3390/toxins8100291 |
_version_ | 1782463772274720768 |
---|---|
author | Starost, Laura Julia Karassek, Sascha Sano, Yasuteru Kanda, Takashi Kim, Kwang Sik Dobrindt, Ulrich Rüter, Christian Schmidt, Marcus Alexander |
author_facet | Starost, Laura Julia Karassek, Sascha Sano, Yasuteru Kanda, Takashi Kim, Kwang Sik Dobrindt, Ulrich Rüter, Christian Schmidt, Marcus Alexander |
author_sort | Starost, Laura Julia |
collection | PubMed |
description | Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood–brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218’s effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB. |
format | Online Article Text |
id | pubmed-5086651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-50866512016-11-02 Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells Starost, Laura Julia Karassek, Sascha Sano, Yasuteru Kanda, Takashi Kim, Kwang Sik Dobrindt, Ulrich Rüter, Christian Schmidt, Marcus Alexander Toxins (Basel) Article Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood–brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218’s effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB. MDPI 2016-10-13 /pmc/articles/PMC5086651/ /pubmed/27754355 http://dx.doi.org/10.3390/toxins8100291 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Starost, Laura Julia Karassek, Sascha Sano, Yasuteru Kanda, Takashi Kim, Kwang Sik Dobrindt, Ulrich Rüter, Christian Schmidt, Marcus Alexander Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells |
title | Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells |
title_full | Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells |
title_fullStr | Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells |
title_full_unstemmed | Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells |
title_short | Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells |
title_sort | pertussis toxin exploits host cell signaling pathways induced by meningitis-causing e. coli k1-rs218 and enhances adherence of monocytic thp-1 cells to human cerebral endothelial cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086651/ https://www.ncbi.nlm.nih.gov/pubmed/27754355 http://dx.doi.org/10.3390/toxins8100291 |
work_keys_str_mv | AT starostlaurajulia pertussistoxinexploitshostcellsignalingpathwaysinducedbymeningitiscausingecolik1rs218andenhancesadherenceofmonocyticthp1cellstohumancerebralendothelialcells AT karasseksascha pertussistoxinexploitshostcellsignalingpathwaysinducedbymeningitiscausingecolik1rs218andenhancesadherenceofmonocyticthp1cellstohumancerebralendothelialcells AT sanoyasuteru pertussistoxinexploitshostcellsignalingpathwaysinducedbymeningitiscausingecolik1rs218andenhancesadherenceofmonocyticthp1cellstohumancerebralendothelialcells AT kandatakashi pertussistoxinexploitshostcellsignalingpathwaysinducedbymeningitiscausingecolik1rs218andenhancesadherenceofmonocyticthp1cellstohumancerebralendothelialcells AT kimkwangsik pertussistoxinexploitshostcellsignalingpathwaysinducedbymeningitiscausingecolik1rs218andenhancesadherenceofmonocyticthp1cellstohumancerebralendothelialcells AT dobrindtulrich pertussistoxinexploitshostcellsignalingpathwaysinducedbymeningitiscausingecolik1rs218andenhancesadherenceofmonocyticthp1cellstohumancerebralendothelialcells AT ruterchristian pertussistoxinexploitshostcellsignalingpathwaysinducedbymeningitiscausingecolik1rs218andenhancesadherenceofmonocyticthp1cellstohumancerebralendothelialcells AT schmidtmarcusalexander pertussistoxinexploitshostcellsignalingpathwaysinducedbymeningitiscausingecolik1rs218andenhancesadherenceofmonocyticthp1cellstohumancerebralendothelialcells |