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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
- Source :
- Toxins, Toxins; Volume 8; Issue 10; Pages: 291, Toxins, Vol 8, Iss 10, p 291 (2016)
- Publication Year :
- 2016
- Publisher :
- MDPI AG, 2016.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 20726651
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Toxins
- Accession number :
- edsair.doi.dedup.....a251279dd44a3f9afe6fad4f43a5b65b
- Full Text :
- https://doi.org/10.3390/toxins8100291