Caspase-11 and AIM2 inflammasome are involved in smoking-induced COPD and lung adenocarcinoma
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Chiara Colarusso1, Michela Terlizzi1, Anne-Sophie Lamort2, Ida Cerqua4, Fiorentina Roviezzo4, Georgios Stathopoulos2,3, Aldo Pinto1 and Rosalinda Sorrentino1
1 Department of Pharmacy (DIFARMA), University of Salerno, Italy
2 Molecular Lung Carcinogenesis Group, Comprehensive Pneumology Center and Institute for Lung Biology and Disease, Ludwig-Maximilians University and Helmholtz Center, Munich, Germany
3 Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Patras, Greece
4 Department of Pharmacy, University of Naples, Italy
Keywords: smoke; COPD; lung cancer; lung inflammation; inflammasome
Received: March 22, 2021 Accepted: May 03, 2021 Published: May 25, 2021
Cigarette smoking is the leading risk factor for COPD and lung cancer establishment. Epidemiologically, COPD patients are 6.35 times more likely to develop lung cancer.
To mimic COPD, we exposed mice to nose-only cigarette smoke and used human samples of lung adenocarcinoma patients according to the smoking and COPD status.
Smoking C57Bl/6N mice had higher enlargement of alveoli, deposition of collagen and mucus production, associated to the release of IL-1-like cytokines, such as IL-1α and IL-1β at early time points and IL-18 at later time points. AIM2 expression was higher in lung recruited dendritic cells and macrophages in smoking mice, associated to the activation of caspase-11, rather than caspase-1. In support,129Sv mice, which are dysfunctional for caspase-11, had lower collagen deposition and mucus production, associated to lower release of IL-1-like and fibrotic TGFβ. Interestingly, higher expression of AIM2 in non-cancerous tissue of smoking COPD adenocarcinoma patients was correlated to a higher hazard ratio of poor survival rate than in patients who presented lower levels of AIM2.
We found that AIM2 inflammasome is at the crossroad between COPD and lung cancer in that its higher presence is correlated to lower survival rate of smoking COPD adenocarcinoma patients.
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