Advanced

Nasal Challenge with LPS Stimulates the Release of Macrophage Inflammatory Protein 1 alpha

Ekman, Anna-Karin LU ; Fransson, Mattias LU ; Rydberg, Camilla; Adner, Mikael LU and Cardell, Lars-Olaf LU (2009) In International Archives of Allergy and Immunology1994-01-01+01:00 149(2). p.154-160
Abstract
Background: Bacterial infections can cause a variety of airway diseases. Toll-like receptors (TLRs) directly respond to the presence of microbes and partake in the innate immune defense. TLR4 is activated by lipopolysaccharide (LPS), and has been detected in sinonasal tissue, epithelial cells and various inflammatory cells. Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a chemokine released during the inflammatory process. The present study investigated the potential role and regulation of MIP-1 alpha in LPS-induced nasal inflammation. Methods: Thirty-two healthy individuals were intranasally challenged with LPS or vehicle. Nasal lavage was performed, followed by a nasal biopsy. Inflammatory cells were counted, MIP-1 alpha levels... (More)
Background: Bacterial infections can cause a variety of airway diseases. Toll-like receptors (TLRs) directly respond to the presence of microbes and partake in the innate immune defense. TLR4 is activated by lipopolysaccharide (LPS), and has been detected in sinonasal tissue, epithelial cells and various inflammatory cells. Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a chemokine released during the inflammatory process. The present study investigated the potential role and regulation of MIP-1 alpha in LPS-induced nasal inflammation. Methods: Thirty-two healthy individuals were intranasally challenged with LPS or vehicle. Nasal lavage was performed, followed by a nasal biopsy. Inflammatory cells were counted, MIP-1 alpha levels analyzed and expression of MIP-1 alpha mRNA in biopsies quantified. Neutrophils isolated from peripheral blood were treated with LPS and effects on MIP1 alpha release, cell survival, and the involved signal pathways, were investigated. Results: LPS challenge caused an increase of MIP-1 alpha in nasal lavage. No corresponding change in mRNA expression was seen in nasal biopsies, suggesting the increase was not due to epithelial synthesis. Neutrophil numbers increased after LPS provocation. Treatment of isolated neutrophils with LPS delayed neutrophil apoptosis and resulted in a time-and concentration-dependent release of MIP-1 alpha, which was reduced by inhibitors of transcription and of nuclear factor (NF)-kappa B, protein kinase C (PKC) and p38 MAPK pathways. Conclusions: Nasal LPS challenge results in release of MIP-1 alpha. The release most likely originates from recruited neutrophils, via NF-kappa B-, PKC-and p38 MAPK-dependent pathways. LPS stimulation delayed neutrophil apop tosis. MIP-1 alpha may constitute an important mediator in neutrophilic airway disease. Copyright (C) 2009 S. Karger AG, Basel (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Nasal, inflammation, Toll-like receptors, Macrophage inflammatory protein-1
in
International Archives of Allergy and Immunology1994-01-01+01:00
volume
149
issue
2
pages
154 - 160
publisher
Karger
external identifiers
  • wos:000263355000010
  • scopus:58149159266
ISSN
1423-0097
DOI
10.1159/000189199
language
English
LU publication?
yes
id
f4137af8-afcb-4bf9-a8fb-bc13b3107536 (old id 1374978)
date added to LUP
2009-05-08 15:34:09
date last changed
2017-06-04 03:46:14
@article{f4137af8-afcb-4bf9-a8fb-bc13b3107536,
  abstract     = {Background: Bacterial infections can cause a variety of airway diseases. Toll-like receptors (TLRs) directly respond to the presence of microbes and partake in the innate immune defense. TLR4 is activated by lipopolysaccharide (LPS), and has been detected in sinonasal tissue, epithelial cells and various inflammatory cells. Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a chemokine released during the inflammatory process. The present study investigated the potential role and regulation of MIP-1 alpha in LPS-induced nasal inflammation. Methods: Thirty-two healthy individuals were intranasally challenged with LPS or vehicle. Nasal lavage was performed, followed by a nasal biopsy. Inflammatory cells were counted, MIP-1 alpha levels analyzed and expression of MIP-1 alpha mRNA in biopsies quantified. Neutrophils isolated from peripheral blood were treated with LPS and effects on MIP1 alpha release, cell survival, and the involved signal pathways, were investigated. Results: LPS challenge caused an increase of MIP-1 alpha in nasal lavage. No corresponding change in mRNA expression was seen in nasal biopsies, suggesting the increase was not due to epithelial synthesis. Neutrophil numbers increased after LPS provocation. Treatment of isolated neutrophils with LPS delayed neutrophil apoptosis and resulted in a time-and concentration-dependent release of MIP-1 alpha, which was reduced by inhibitors of transcription and of nuclear factor (NF)-kappa B, protein kinase C (PKC) and p38 MAPK pathways. Conclusions: Nasal LPS challenge results in release of MIP-1 alpha. The release most likely originates from recruited neutrophils, via NF-kappa B-, PKC-and p38 MAPK-dependent pathways. LPS stimulation delayed neutrophil apop tosis. MIP-1 alpha may constitute an important mediator in neutrophilic airway disease. Copyright (C) 2009 S. Karger AG, Basel},
  author       = {Ekman, Anna-Karin and Fransson, Mattias and Rydberg, Camilla and Adner, Mikael and Cardell, Lars-Olaf},
  issn         = {1423-0097},
  keyword      = {Nasal,inflammation,Toll-like receptors,Macrophage inflammatory protein-1},
  language     = {eng},
  number       = {2},
  pages        = {154--160},
  publisher    = {Karger},
  series       = {International Archives of Allergy and Immunology1994-01-01+01:00},
  title        = {Nasal Challenge with LPS Stimulates the Release of Macrophage Inflammatory Protein 1 alpha},
  url          = {http://dx.doi.org/10.1159/000189199},
  volume       = {149},
  year         = {2009},
}