The role of the CCR1 receptor in the inflammatory response to tobacco smoke in a mouse model
| Autor: | Martin R. Stämpfli, Naila Svitacheva, Kerstin Thim, Maria Lindahl, John D. Taylor, Per Ola Önnervik, Amir Smailagic, Robert Virtala |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Lipopolysaccharides
CCR1 Allergy Immunology Receptors CCR1 Tobacco smoke induced inflammation Gene Expression Inflammation Disease Tobacco smoke Mice Smoke Tobacco Animals Humans Medicine Receptor Steroid Pathological Mice Knockout C chemokine receptor 1 Pharmacology Mice Inbred BALB C business.industry Chronic obstructive pulmonary disease food and beverages medicine.disease Original Research Paper Female Steroids sense organs medicine.symptom business Bronchoalveolar Lavage Fluid |
| Zdroj: | Inflammation Research |
| ISSN: | 1023-3830 |
| DOI: | 10.1007/s00011-010-0193-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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