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
| Autor: | Ulrich Dobrindt, Marcus Alexander Schmidt, Laura Starost, Takashi Kanda, Christian Rüter, Sascha Karassek, Yasuteru Sano, Kwang Sik Kim |
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| Rok vydání: | 2016 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine Bordetella pertussis Meningitis Escherichia coli Health Toxicology and Mutagenesis lcsh:Medicine Chromosomal translocation blood–brain barrier Toxicology medicine.disease_cause Pertussis toxin p38 Mitogen-Activated Protein Kinases Article NF-κB Monocytes Virulence factor Cell Line Microbiology NMEC 03 medical and health sciences chemistry.chemical_compound Cell Adhesion Escherichia coli medicine MAPK p38 Humans THP1 cell line RNA Messenger Phosphorylation Cerebrum pertussis toxin biology lcsh:R NF-kappa B Endothelial Cells Intercellular Adhesion Molecule-1 biology.organism_classification neonatal meningitis-causing E. coli K1-RS218 030104 developmental biology chemistry Cytokines Signal transduction Signal Transduction |
| Zdroj: | Toxins Toxins; Volume 8; Issue 10; Pages: 291 Toxins, Vol 8, Iss 10, p 291 (2016) |
| ISSN: | 2072-6651 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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