Cigarette Smoke Triggers IL-33–associated Inflammation in a Model of Late-Stage Chronic Obstructive Pulmonary Disease
| Autor: | Jasmine Lee, Kendra L. Hailey, Timothy D. Bigby, Steven A. Vitorino, Ellen C. Breen, Patricia A. Jennings |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Respiratory System Clinical Biochemistry Cardiorespiratory Medicine and Haematology alveolar epithelial cells Mice chemistry.chemical_compound 0302 clinical medicine 2.1 Biological and endogenous factors Cigarette smoke Aetiology Lung Cardiopulmonary disease COPD vascular endothelial growth factor alarmins Smoking Vascular endothelial growth factor Infectious Diseases Respiratory Cytokines medicine.symptom Pulmonary and Respiratory Medicine Chronic Obstructive Chronic Obstructive Pulmonary Disease Pulmonary disease Inflammation Proinflammatory cytokine Pulmonary Disease 03 medical and health sciences Tobacco medicine Animals Humans Molecular Biology Tobacco Smoke and Health business.industry Macrophages Cell Biology Interleukin-33 ST2 medicine.disease Interleukin 33 030104 developmental biology 030228 respiratory system chemistry Immunology business |
| Zdroj: | American journal of respiratory cell and molecular biology, vol 61, iss 5 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/rcmb.2018-0402oc |
| Popis: | Chronic obstructive pulmonary disease (COPD) is a worldwide threat. Cigarette smoke (CS) exposure causes cardiopulmonary disease and COPD and increases the risk for pulmonary tumors. In addition to poor lung function, patients with COPD are susceptible to bouts of dangerous inflammation triggered by pollutants or infection. These severe inflammatory episodes can lead to additional exacerbations, hospitalization, further deterioration of lung function, and reduced survival. Suitable models of the inflammatory conditions associated with CS, which potentiate the downward spiral in patients with COPD, are lacking, and the underlying mechanisms that trigger exacerbations are not well understood. Although initial CS exposure activates a protective role for vascular endothelial growth factor (VEGF) functions in barrier integrity, chronic exposure depletes the pulmonary VEGF guard function in severe COPD. Thus, we hypothesized that mice with compromised VEGF production and challenged with CS would trigger human-like severe inflammatory progression of COPD. In this model, we discovered that CS exposure promotes an amplified IL-33 cytokine response and severe disease progression. Our VEGF-knockout model combined with CS recapitulates severe COPD with an influx of IL-33-expressing macrophages and neutrophils. Normally, IL-33 is quickly inactivated by a post-translational disulfide bond formation. Our results reveal that BAL fluid from the CS-exposed, VEGF-deficient cohort promotes a significantly prolonged lifetime of active proinflammatory IL-33. Taken together, our data demonstrate that with the loss of a VEGF-mediated protective barrier, the CS response switches from a localized danger to an uncontrolled long-term and long-range, amplified, IL-33-mediated inflammatory response that ultimately destroys lung function. |
| Databáze: | OpenAIRE |
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