Modulators of Cigarette Smoke–Induced Pulmonary Emphysema in A/J Mice

March, Thomas H.; Wilder, Julie A.; Esparza, D.; Cossey, Patsy Y.; Blair, Lee F.; Herrera, Lois K.; McDonald, Jacob D.; Campen, Matthew J.; Mauderly, Joe L.; Seagrave, JeanClare

doi:10.1093/toxsci/kfl016

Cited by 119 publications

(104 citation statements)

References 34 publications

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“…Neutrophils and lymphocytes have been reported to persist in lungs of chronic CS-exposed mice after smoking cessation (33,34). Remarkably, our data in WT mice show that subacute CS exposure sufficed to sustain neutrophilic inflammation and elevated levels of the neutrophil attractant CXCL1 in the lung, for at least 2 wk after smoking cessation.…”

Section: Dcs In Chemr23supporting

confidence: 53%

The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation

Demoor

Bracke

Dupont

et al. 2011

The Journal of Immunology

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Chronic obstructive pulmonary disease is mainly triggered by cigarette smoke (CS) and progresses even after smoking cessation. CS induces an exaggerated influx of inflammatory cells to the bronchoalveolar space and lung parenchyma, likely resulting from a complex interplay between chemoattractants and their respective receptors. In a murine CS model of chronic obstructive pulmonary disease, we studied the importance of chemokine-like receptor ChemR23 for the induction and resolution of inflammation in CS-exposed lungs. Subacute and chronic CS exposure increased protein levels of the ChemR23 ligand and chemoattractant, chemerin, in bronchoalveolar lavage (BAL) fluid of wild-type (WT) mice. Moreover, the proinflammatory chemokines CXCL1, CCL2, and CCL20 were increased in the airways of CS-exposed WT mice, accompanied by a massive accumulation of inflammatory neutrophils and monocytes, CD11bhiCD103− and CD11bloCD103+ dendritic cells (DCs), and CD4+ and CD8+ T cells. The lung parenchyma of WT mice was infiltrated with inflammatory neutrophils, CD11bhiCD103− DCs, and activated CD4+ T cells after CS exposure. CS-induced inflammation was severely attenuated in BAL fluid and lungs of ChemR23 knockout mice with regard to the induction of inflammatory chemokines and the recruitment of inflammatory cells. Neutrophils and CD8+ T cells persisted in the airways of WT mice, as did the airway-derived conventional DCs in the mediastinal lymph nodes, for at least 14 d after smoking cessation. In the BAL fluid of CS-exposed ChemR23 knockout mice, there was a remarkable delayed accumulation of T cells 14 d after the final exposure. Our data support a role for ChemR23 in directing innate and adaptive immune cells to CS-exposed lungs.

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Section: Dcs In Chemr23supporting

confidence: 53%

The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation

Demoor

Bracke

Dupont

et al. 2011

The Journal of Immunology

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“…Female A/J mice were exposed to dilute mainstream cigarette smoke for 5 days/week for 12 weeks. 24 Groups of mice were treated with AT-RvD1 twice a week either by inhalation or by i.v. injection as described in Materials and Methods.…”

Section: At-rvd1 Inhibits Long-term Cigarette Smokeeinduced Airspace mentioning

confidence: 99%

Resolvin D1 Reduces Emphysema and Chronic Inflammation

Hsiao

Thatcher

Colas

et al. 2015

The American Journal of Pathology

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Chronic obstructive pulmonary disease is characterized, in part, by chronic inflammation that persists even after smoking cessation, suggesting that a failure to resolve inflammation plays an important role in the pathogenesis of the disease. It is widely recognized that the resolution of inflammation is an active process, governed by specialized proresolving lipid mediators, including lipoxins, resolvins, maresins, and protectins. Here, we report that proresolving signaling and metabolic pathways are disrupted in lung tissue from patients with chronic obstructive pulmonary disease, suggesting that supplementation with proresolving lipid mediators might reduce the development of emphysema by controlling chronic inflammation. Groups of mice were exposed long-term to cigarette smoke and treated with the proresolving mediator resolvin D1. Resolvin D1 was associated with a reduced development of cigarette smokeeinduced emphysema and airspace enlargement, with concurrent reductions in inflammation, oxidative stress, and cell death. Interestingly, resolvin D1 did not promote the differentiation of M2 macrophages and did not promote tissue fibrosis. Taken together, our results suggest that cigarette smoking disrupts endogenous proresolving pathways and that supplementation with specialized proresolving lipid mediators is an important therapeutic strategy in chronic lung disease, especially if endogenous specialized proresolving lipid mediator signaling is impaired. (Am J Pathol 2015, 185: 3189e3201; http:// dx.doi.org/10.1016/j.ajpath.2015 Chronic obstructive pulmonary disease (COPD) is a major global health problem and a leading cause of death and disability. Tobacco smoking remains the major causative factor in the development of COPD; however, new evidence suggests that household air pollution from fuel used for indoor cooking and heating is also a significant cause.

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“…Therefore, cigarettes should be tested in in vivo models of cigarette smoke-induced inflammation, chronic bronchitis, and emphysema, as has been done previously (Fields et al, 2005;March et al, 2006;Nikula et al, 2000;Seagrave et al, 2004). …”

Section: Csc-induced Gene Expression In Airway Epitheliamentioning

confidence: 99%

Effects Of 10 Cigarette Smoke Condensates On Primary Human Airway Epithelial Cells By Comparative Gene And Cytokine Expression Studies

Pickett¹,

Seagrave²,

Boggs³

et al. 2010

D23. Recent Advances on Smoking Health Effects

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Cigarettes vary in tobacco blend, filter ventilation, additives, and other physical and chemical properties, but little is known regarding potential differences in toxicity to a smoker's airway epithelia. We compared changes in gene expression and cytokine production in primary normal human bronchial epithelial cells following treatment for 18 h with cigarette smoke condensates (CSCs) prepared from five commercial and four research cigarettes, at doses of~4 mg/ml nicotine. Nine of the CSCs were produced under a standard International Organization for Standardization smoking machine regimen and one was produced by a more intense smoking machine regimen. Isolated messenger RNA (mRNA) was analyzed by microarray hybridization, and media was analyzed for secreted cytokines and chemokines. Twenty-one genes were differentially expressed by at least 9 of the 10 CSCs by more than twofold, including genes encoding detoxifying and antioxidant proteins. Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and NAD(P)H dehydrogenase, quinone 1 (NQO-1) were selected for validation with quantitative real-time PCR (qRT-PCR) and Western blot analyses. NQO-1 expression determined with microarrays, qRT-PCR, and Western blotting differed among the CSC types, with good correlation among the different assays. CYP1A1 mRNA levels varied substantially, but there was little correlation with the protein levels. For each CSC, the three most induced and three most repressed genes were identified. These genes may be useful as markers of exposure to that particular cigarette type. Furthermore, differences in interleukin-8 secretion were observed. These studies lay the foundation for future investigations to analyze differences in the responses of in vivo systems to tobacco products marketed with claims of reduced exposure or reduced harm.

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Modulators of Cigarette Smoke–Induced Pulmonary Emphysema in A/J Mice

Cited by 119 publications

References 34 publications

The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation

The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation

Resolvin D1 Reduces Emphysema and Chronic Inflammation

Effects Of 10 Cigarette Smoke Condensates On Primary Human Airway Epithelial Cells By Comparative Gene And Cytokine Expression Studies

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