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The role of the CCR1 receptor in the inflammatory response to tobacco smoke in a mouse model

Önnervik, Per Ola ; Lindahl, Maria ; Svitacheva, Naila LU ; Stämpfli, Martin ; Thim, Kerstin ; Smailagic, Amir ; Virtala, Robert and Taylor, John D. (2010) In Inflammation Research 59(10). p.817-825
Abstract

Objective: The aim was to create pathological changes in mice relevant to human smoke exposure that can be used to further understand the mechanisms and pathology of smoke-induced inflammatory disease. Methods: Mice were exposed to tobacco smoke or lipopolysaccharide (LPS) to generate an inflammatory infiltrate within the lungs. Results: Tobacco smoke exposure over a 4 day period led to neutrophilia in the lungs of BALB/c mice. Within the inflammatory exudates, significant changes were also seen in protein levels of IL-1B, IL-6, MIP-2, KC (IL-8) and TIMP-1 as measured by ELISA. Further protein changes, as measured via multiplex analysis revealed increased levels of MMP-9, MDC, LIF and MCP-1, amongst other mediators. Major changes in... (More)

Objective: The aim was to create pathological changes in mice relevant to human smoke exposure that can be used to further understand the mechanisms and pathology of smoke-induced inflammatory disease. Methods: Mice were exposed to tobacco smoke or lipopolysaccharide (LPS) to generate an inflammatory infiltrate within the lungs. Results: Tobacco smoke exposure over a 4 day period led to neutrophilia in the lungs of BALB/c mice. Within the inflammatory exudates, significant changes were also seen in protein levels of IL-1B, IL-6, MIP-2, KC (IL-8) and TIMP-1 as measured by ELISA. Further protein changes, as measured via multiplex analysis revealed increased levels of MMP-9, MDC, LIF and MCP-1, amongst other mediators. Major changes in whole lung tissue gene expression patterns were observed. The neutrophilia seen after smoke exposure was steroid-insensitive, relative to doses of steroid needed to reduce LPS-driven neutrophilia in controls. This exposes pathological switches that are changed upon exposure to tobacco smoke, rendering steroids less effective under these conditions. Challenge of chemokine receptor type 1 (CCR1) KO mice in the tobacco smoke model showed that lack of this gene protected the mice from smoke-induced inflammation. Conclusions: This suggests the CCR1 receptor has a key role in the pathogenesis of smoke-induced inflammation.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C chemokine receptor 1, Chronic obstructive pulmonary disease, Steroid, Tobacco smoke induced inflammation
in
Inflammation Research
volume
59
issue
10
pages
817 - 825
publisher
Birkhäuser
external identifiers
  • pmid:20387089
  • scopus:77956938867
ISSN
1023-3830
DOI
10.1007/s00011-010-0193-5
language
English
LU publication?
no
id
29301022-16eb-470f-9e7d-0123de792ce3
date added to LUP
2020-02-25 16:43:23
date last changed
2024-04-03 01:54:37
@article{29301022-16eb-470f-9e7d-0123de792ce3,
  abstract     = {{<p>Objective: The aim was to create pathological changes in mice relevant to human smoke exposure that can be used to further understand the mechanisms and pathology of smoke-induced inflammatory disease. Methods: Mice were exposed to tobacco smoke or lipopolysaccharide (LPS) to generate an inflammatory infiltrate within the lungs. Results: Tobacco smoke exposure over a 4 day period led to neutrophilia in the lungs of BALB/c mice. Within the inflammatory exudates, significant changes were also seen in protein levels of IL-1B, IL-6, MIP-2, KC (IL-8) and TIMP-1 as measured by ELISA. Further protein changes, as measured via multiplex analysis revealed increased levels of MMP-9, MDC, LIF and MCP-1, amongst other mediators. Major changes in whole lung tissue gene expression patterns were observed. The neutrophilia seen after smoke exposure was steroid-insensitive, relative to doses of steroid needed to reduce LPS-driven neutrophilia in controls. This exposes pathological switches that are changed upon exposure to tobacco smoke, rendering steroids less effective under these conditions. Challenge of chemokine receptor type 1 (CCR1) KO mice in the tobacco smoke model showed that lack of this gene protected the mice from smoke-induced inflammation. Conclusions: This suggests the CCR1 receptor has a key role in the pathogenesis of smoke-induced inflammation.</p>}},
  author       = {{Önnervik, Per Ola and Lindahl, Maria and Svitacheva, Naila and Stämpfli, Martin and Thim, Kerstin and Smailagic, Amir and Virtala, Robert and Taylor, John D.}},
  issn         = {{1023-3830}},
  keywords     = {{C chemokine receptor 1; Chronic obstructive pulmonary disease; Steroid; Tobacco smoke induced inflammation}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{10}},
  pages        = {{817--825}},
  publisher    = {{Birkhäuser}},
  series       = {{Inflammation Research}},
  title        = {{The role of the CCR1 receptor in the inflammatory response to tobacco smoke in a mouse model}},
  url          = {{http://dx.doi.org/10.1007/s00011-010-0193-5}},
  doi          = {{10.1007/s00011-010-0193-5}},
  volume       = {{59}},
  year         = {{2010}},
}