1. Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD.
- Author
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Pauwels NS, Bracke KR, Dupont LL, Van Pottelberge GR, Provoost S, Vanden Berghe T, Vandenabeele P, Lambrecht BN, Joos GF, and Brusselle GG
- Subjects
- Animals, Antibodies, Neutralizing pharmacology, Bronchoalveolar Lavage Fluid chemistry, Bronchoalveolar Lavage Fluid cytology, Humans, Inflammation, Interleukin-1alpha antagonists & inhibitors, Interleukin-1beta antagonists & inhibitors, Lung pathology, Macrophages pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Neutrophils pathology, Pulmonary Disease, Chronic Obstructive etiology, Pulmonary Disease, Chronic Obstructive pathology, Receptors, Interleukin-1 metabolism, Tobacco Smoke Pollution adverse effects, Adaptor Proteins, Signal Transducing metabolism, Apoptosis Regulatory Proteins metabolism, Caspase 1 metabolism, Interleukin-1alpha metabolism, Interleukin-1beta metabolism, Pulmonary Disease, Chronic Obstructive physiopathology, Smoking adverse effects
- Abstract
Cigarette smoke (CS), the primary risk factor of chronic obstructive pulmonary disease (COPD), leads to pulmonary inflammation through interleukin-1 receptor (IL-1R)I signalling, as determined using COPD mouse models. It is unclear whether interleukin (IL)-1α or IL-1β, activated by the Nlrp3/caspase-1 axis, is the predominant ligand for IL-1RI in CS-induced responses. We exposed wild-type mice (treated with anti-IL-1α or anti-IL-1β antibodies), and IL-1RI knockout (KO), Nlrp3 KO and caspase-1 KO mice to CS for 3 days or 4 weeks and evaluated pulmonary inflammation. Additionally, we measured the levels of IL-1α and IL-1β mRNA (in total lung tissue by RT-PCR) and protein (in induced sputum by ELISA) of never-smokers, smokers without COPD and patients with COPD. In CS-exposed mice, pulmonary inflammation was dependent on IL-1RI and could be significantly attenuated by neutralising IL-1α or IL-1β. Interestingly, CS-induced inflammation occurred independently of IL-1β activation by the Nlrp3/caspase-1 axis. In human subjects, IL-1α and IL-1β were significantly increased in total lung tissue and induced sputum of patients with COPD, respectively, compared with never-smokers. These results suggest that not only IL-1β but also IL-1α should be considered as an important mediator in CS-induced inflammation and COPD.
- Published
- 2011
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