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Epidermal growth factor receptor signaling enhances the proinflammatory effects of staphylococcus aureus gamma-toxin on the mucosa
- Source :
- Toxins; Volume 9; Issue 7; Pages: 202, Toxins
- Publication Year :
- 2017
- Publisher :
- MDPI, 2017.
-
Abstract
- Source at https://doi.org/10.3390/toxins9070202. Staphylococcus aureus (S. aureus) produces many different exotoxins including the gamma-toxins, HlgAB and HlgCB. Gamma-toxins form pores in both leukocyte and erythrocyte membranes, resulting in cell lysis. The genes encoding gamma-toxins are present in most strains of S. aureus, and are commonly expressed in clinical isolates recovered from menstrual Toxic Shock Syndrome (mTSS) patients. This study set out to investigate the cytotoxic and proinflammatory effects of gamma-toxins on vaginal epithelial surfaces. We found that both HlgAB and HlgCB were cytotoxic to cultured human vaginal epithelial cells (HVECs) and induced cytokine production at sub-cytotoxic doses. Cytokine production induced by gamma-toxin treatment of HVECs was found to involve epidermal growth factor receptor (EGFR) signaling and mediated by shedding of EGFR ligands from the cell surface. The gamma-toxin subunits displayed differential binding to HVECs (HlgA 93%, HlgB 97% and HlgC 28%) with both components (HlgAB or HlgCB) required for maximum detectable binding and significant stimulation of cytokine production. In studies using full thickness ex vivo porcine vaginal mucosa, HlgAB or HlgCB stimulated a dose-dependent cytokine response, which was reduced significantly by inhibition of EGFR signaling. The effects of gamma-toxins on porcine vaginal tissue and cultured HVECs were validated using ex vivo human ectocervical tissue. Collectively, these studies have identified the EGFR-signaling pathway as a key component in gamma-toxin-induced proinflammatory changes at epithelial surfaces and highlight a potential therapeutic target to diminish toxigenic effects of S. aureus infections.
- Subjects :
- 0301 basic medicine
Erythrocytes
Swine
Health, Toxicology and Mutagenesis
medicine.medical_treatment
Cell
Cervix Uteri
Toxicology
medicine.disease_cause
Menstrual toxic shock syndrome
Hemolysin Proteins
Staphylococcus aureus
gamma-toxin
epidermal growth factor receptor
menstrual toxic shock syndrome
tyrosine kinase inhibitors
and mucosal immune response
VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Klinisk farmakologi: 739
Cytotoxic T cell
Epidermal growth factor receptor
biology
VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical microbiology: 715
ErbB Receptors
Cytokine
medicine.anatomical_structure
VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk mikrobiologi: 715
Vagina
Cytokines
Female
Rabbits
Mucosal immune response
Signal Transduction
VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Clinical pharmacology: 739
030106 microbiology
Bacterial Toxins
Gamma-toxin
Hemolysis
Article
Microbiology
Proinflammatory cytokine
03 medical and health sciences
Bacterial Proteins
medicine
Animals
Humans
Inflammation
Tyrosine kinase inhibitors
Mucous Membrane
Toxic shock syndrome
Epithelial Cells
medicine.disease
030104 developmental biology
biology.protein
Ex vivo
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Toxins; Volume 9; Issue 7; Pages: 202, Toxins
- Accession number :
- edsair.doi.dedup.....5c9ab3d7511f4b17e5b083ff78f6ec92