The role of the CCR1 receptor in the inflammatory response to tobacco smoke in a mouse model
(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
- Önnervik, Per Ola ; Lindahl, Maria ; Svitacheva, Naila LU ; Stämpfli, Martin ; Thim, Kerstin ; Smailagic, Amir ; Virtala, Robert and Taylor, John D.
- publishing date
- 2010-10-01
- 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}}, }