Journal Article

AIM2 Inflammasome Activation Leads to IL-1α and TGF-β Release From Exacerbated Chronic Obstructive Pulmonary Disease-Derived Peripheral Blood Mononuclear Cells

Rega, Roberto, Colarusso, Chiara, Saccomanno, Antonello, Terlizzi, Michela, Sorrentino, Rosalinda, Pinto, Aldo, Aquino, Rita P., Molino, Antonio, Somma, Pasquale, Imitazione, Pasquale

2019

Overview

Chronic obstructive pulmonary disease (COPD) is now the fourth-leading cause of death worldwide and its prevalence is increasing. The progressive decline of lung function and airway remodelling are a consequence of chronic inflammatory responses. It was recently postulated the involvement of the inflammasome in COPD, although the underlying mechanism/s still need to be elucidated. Therefore, we isolated peripheral blood mononuclear cells (PBMCs) from exacerbated/unstable COPD patients. The stimulation of PBMCs with an AIM2 inflammasome activator, Poly dA:dT, led to IL-1α, but not IL-1β, release. The release of this cytokine was caspase-1- and caspase-4-dependent and correlated to higher levels of 8-OH-dG in COPD compared to non-smoker and smoker-derived PBMCs. Interestingly, AIM2-depedent IL-1α release was responsible for higher TGF-β levels, crucial mediator during pro-fibrotic processes associated to COPD progression. In conclusion, our data highlight the involvement of AIM2/caspase-1/caspase-4 in IL-1α-induced TGF-β release in unstable COPD-derived PBMCs, opening new therapeutic perspectives for unstable COPD patients.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Caspase-1 / Caspase-4 / chronic lung inflammation / Chronic obstructive pulmonary disease / COPD / Cytokines / fibrosis / Flow cytometry / IL-1-like cytokines / inflammasome / Inflammasomes / Inflammation / Leukocytes (mononuclear) / Lung diseases / Oxidative stress / Peripheral blood mononuclear cells / Pharmacology / Respiratory function / Transforming growth factor-b