Cigarette Smoke Triggers IL-33–associated Inflammation in a Model of Late-Stage Chronic Obstructive Pulmonary Disease

What is it about?

CS pollutant exposure is common and causes lung destruction via poorly understood inflammatory mechanisms that progress to end-stage COPD. Activation of VEGF is the first response to sudden contact with pollutants. However, chronic exposure results in downregulation of VEGF. The main barrier to battling COPD is the lack of a model recapitulating the VEGF-dependent progression to end-stage inflammatory disease. We present a VEGF-deficient COPD model that overcomes this scientific barrier. These mice have a weakened protective lung barrier and display amplified inflammation upon CS exposure. This response is mediated by upregulation and prolonged activation of the pro-inflammatory cytokine IL-33. Our data reveal a robust model for future studies and implicate prolonged IL-33 signaling as a therapeutic target in COPD.

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