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M1 protein of Streptococcus pyogenes increases production of the antibacterial CXC chemokine MIG/CXCL9 in pharyngeal epithelial cells

Eliasson, Mette LU ; Frick, Inga-Maria LU ; Collin, Mattias LU ; Sørensen, Ole E LU ; Björck, Lars LU and Egesten, Arne LU (2007) In Microbial Pathogenesis 43(5-6). p.224-233
Abstract
Streptococcus pyogenes adheres to epithelial cells of the human pharynx where it can cause pharyngitis. To counteract infection. inflamed epithelium produces peptide antibiotics, among them the CXC chemokine MIG/CXCL9. M protein is both a surface-associated and released virulence factor of S. pyogenes. Here we show that soluble M1 protein enhances MIG gene expression and synthesis in IFN-gamma stimulated epithelial cells. M1 protein was recognized both by resting and IFN-gamma activated pharyngeal epithelial cells as detected by activation of the transcription factor NF-kappa B. Furthermore, pharmacological inhibition of NF-kappa B. decreased MIG synthesis in IFN-gamma activated cells, demonstrating a key role for NF-kappa B in mediating... (More)
Streptococcus pyogenes adheres to epithelial cells of the human pharynx where it can cause pharyngitis. To counteract infection. inflamed epithelium produces peptide antibiotics, among them the CXC chemokine MIG/CXCL9. M protein is both a surface-associated and released virulence factor of S. pyogenes. Here we show that soluble M1 protein enhances MIG gene expression and synthesis in IFN-gamma stimulated epithelial cells. M1 protein was recognized both by resting and IFN-gamma activated pharyngeal epithelial cells as detected by activation of the transcription factor NF-kappa B. Furthermore, pharmacological inhibition of NF-kappa B. decreased MIG synthesis in IFN-gamma activated cells, demonstrating a key role for NF-kappa B in mediating the enhanced response. Microarrays were used to investigate expression of recognized antimicrobial peptides in pharyngeal epithelial cells after stimulation with a combination of IFN-gamma and M1 protein. Amongst the most up-regulated and expressed genes, were several antibacterial CC and CXC chemokines. To investigate all in vivo context, pharyngeal mucosa was stimulated in vitro and MIG could be detected by immunohistochemistry in epithelial cells. The results show that epithelial cells can recognize solubilized M I protein and intact S. pyogenes, thereby modulating an antibacterial innate host response that may have bearing oil the outcome of streptococcal pharyngitis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
innate immunity, mucosa, infection
in
Microbial Pathogenesis
volume
43
issue
5-6
pages
224 - 233
publisher
Academic Press
external identifiers
  • wos:000250194800007
  • scopus:34548624932
ISSN
1096-1208
DOI
10.1016/j.micpath.2007.06.007
language
English
LU publication?
yes
id
634f694e-9b8a-46fa-a520-23480ab2f893 (old id 655151)
date added to LUP
2007-12-10 15:52:35
date last changed
2017-01-01 05:01:16
@article{634f694e-9b8a-46fa-a520-23480ab2f893,
  abstract     = {Streptococcus pyogenes adheres to epithelial cells of the human pharynx where it can cause pharyngitis. To counteract infection. inflamed epithelium produces peptide antibiotics, among them the CXC chemokine MIG/CXCL9. M protein is both a surface-associated and released virulence factor of S. pyogenes. Here we show that soluble M1 protein enhances MIG gene expression and synthesis in IFN-gamma stimulated epithelial cells. M1 protein was recognized both by resting and IFN-gamma activated pharyngeal epithelial cells as detected by activation of the transcription factor NF-kappa B. Furthermore, pharmacological inhibition of NF-kappa B. decreased MIG synthesis in IFN-gamma activated cells, demonstrating a key role for NF-kappa B in mediating the enhanced response. Microarrays were used to investigate expression of recognized antimicrobial peptides in pharyngeal epithelial cells after stimulation with a combination of IFN-gamma and M1 protein. Amongst the most up-regulated and expressed genes, were several antibacterial CC and CXC chemokines. To investigate all in vivo context, pharyngeal mucosa was stimulated in vitro and MIG could be detected by immunohistochemistry in epithelial cells. The results show that epithelial cells can recognize solubilized M I protein and intact S. pyogenes, thereby modulating an antibacterial innate host response that may have bearing oil the outcome of streptococcal pharyngitis.},
  author       = {Eliasson, Mette and Frick, Inga-Maria and Collin, Mattias and Sørensen, Ole E and Björck, Lars and Egesten, Arne},
  issn         = {1096-1208},
  keyword      = {innate immunity,mucosa,infection},
  language     = {eng},
  number       = {5-6},
  pages        = {224--233},
  publisher    = {Academic Press},
  series       = {Microbial Pathogenesis},
  title        = {M1 protein of Streptococcus pyogenes increases production of the antibacterial CXC chemokine MIG/CXCL9 in pharyngeal epithelial cells},
  url          = {http://dx.doi.org/10.1016/j.micpath.2007.06.007},
  volume       = {43},
  year         = {2007},
}