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Updated: Aug 11, 2026
Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System
Published on: October 22, 2020
Involvement of MMP-12 and phosphodiesterase type 4 in cigarette smoke-induced inflammation in mice
O Leclerc1, V Lagente, J-M Planquois
1INSERM U620, Université de Rennes 1, 2, avenue du Professeur Léon Bernard, 35043 Rennes cedex, France. vincent.lagente@univ-rennes1.fr
Abstract:
The aim of the present study was to characterise a mouse model of airways inflammation induced by cigarette smoke and to compare it with a lipopolysaccharide (LPS) model with regards to the efficacy of a PDE4 inhibitor (cilomilast), a corticosteroid (dexamethasone) and macrophage metalloelastase (MMP)-12 gene deletion. Cigarette smoke exposure for 3 days induced a time-dependent airway neutrophilia associated with an increased level of keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP)-2, MIP-1alpha and MMP-9 in the bronchoalveolar lavage (BAL). LPS exposure also induced an increase in the number of neutrophils in BAL. Studies in MMP-12-/- mice showed that in contrast to the smoking model, MMP-12 did not have a critical role in LPS-induced inflammation. Both cilomilast and dexamethasone blocked LPS-induced neutrophilia in a dose-dependent manner. Cilomilast inhibited cigarette smoke-induced neutrophilia and MIP-1alpha, but only 10 mg.kg(-1) of dexamethasone was effective. Both anti-inflammatory treatments had no effect on the levels of KC and MIP-2 in the BAL. Although the inflammatory response was very similar in the smoking model and LPS, the pharmacological modulation and the MMP-12 gene deletion highlighted the differences in the mechanisms involved. Furthermore, the cigarette smoke model seemed to better represent the situation described in chronic obstructive pulmonary disease patients. In conclusion, these differences underline the importance of using an acute smoke-exposure model to investigate potential new treatments for chronic obstructive pulmonary disease.
Insights
This study compared cigarette smoke and lipopolysaccharide (LPS) models of airway inflammation. The cigarette smoke model better reflects chronic obstructive pulmonary disease (COPD), suggesting its utility for testing new COPD treatments.
Area of Science:
- Pulmonary Medicine
- Inflammation Research
- Pharmacology
Background:
- Airways inflammation is central to chronic obstructive pulmonary disease (COPD).
- Mouse models are crucial for understanding inflammatory mechanisms and testing therapeutics.
- Comparing different models helps elucidate disease-specific pathways.
Purpose of the Study:
- To characterize a mouse model of airway inflammation induced by cigarette smoke.
- To compare the cigarette smoke model with a lipopolysaccharide (LPS)-induced inflammation model.
- To evaluate the efficacy of anti-inflammatory agents (cilomilast, dexamethasone) and MMP-12 gene deletion in these models.
Main Methods:
- Induction of airway inflammation via cigarette smoke exposure or LPS administration in mice.
- Assessment of inflammatory cell influx (neutrophils) and mediator levels (chemokines, MMP-9) in bronchoalveolar lavage (BAL) fluid.
- Pharmacological treatment with PDE4 inhibitor (cilomilast) and corticosteroid (dexamethasone).
- Evaluation using macrophage metalloelastase (MMP)-12 gene-deleted (MMP-12-/-) mice.
Main Results:
- Cigarette smoke induced time-dependent neutrophilia and elevated KC, MIP-2, MIP-1alpha, and MMP-9 levels.
- LPS also induced neutrophilia, but MMP-12 was not critical in this model.
- Cilomilast and dexamethasone effectively reduced LPS-induced neutrophilia.
- Cilomilast inhibited smoke-induced neutrophilia and MIP-1alpha; dexamethasone showed partial efficacy.
- Neither drug affected KC and MIP-2 levels in BAL from smoke-exposed mice.
- Pharmacological modulation and MMP-12 deletion revealed distinct mechanisms between the models.
Conclusions:
- The cigarette smoke model more closely resembles the inflammatory situation in COPD patients than the LPS model.
- Differences in inflammatory mediator profiles and drug responses highlight distinct pathogenic mechanisms.
- Acute smoke-exposure models are important for investigating novel COPD treatments.
