Cigarette Smoke Triggers IL-33-Associated Inflammation in a Model of Late Stage COPD.

08:00 EDT 11th April 2019 | BioPortfolio

Summary of "Cigarette Smoke Triggers IL-33-Associated Inflammation in a Model of Late Stage COPD."

Chronic Obstructive Pulmonary Disease (COPD) is a worldwide threat. Cigarette smoke (CS) exposure causes cardiopulmonary disease, COPD and increases the risk for pulmonary tumors. In addition to poor lung function, those 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 COPD patients, are lacking and the underlying mechanisms that trigger exacerbations are not well understood. While initial CS exposure activates a protective role for vascular endothelial growth factor (VEGF) functions in barrier integrity, chronic exposure depletes 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 progressions of COPD. In this model, we discovered that CS exposure promotes an amplified Interleukin-33 (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 (DSB) formation. Our results reveal that bronchoalveolar lavage fluid (BALF) from the CS-exposed, VEGF-deficient cohort promotes a significantly prolonged lifetime of active pro-inflammatory 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.


Journal Details

This article was published in the following journal.

Name: American journal of respiratory cell and molecular biology
ISSN: 1535-4989


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