Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD.

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.

• Authors: N S Pauwels, K R Bracke, L L Dupont, G R Van Pottelberge, S Provoost, T Vanden Berghe, P Vandenabeele, B N Lambrecht, G F Joos, G G Brusselle
• Journal: The European respiratory journal (Eur Respir J) Vol. 38 Issue 5 Pg. 1019-28 (Nov 2011) ISSN: 1399-3003 [Electronic] England
• PMID: 21622588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Antibodies, Neutralizing
• Apoptosis Regulatory Proteins
• Interleukin-1alpha
• Interleukin-1beta
• NALP1 protein, mouse
• Receptors, Interleukin-1
• Tobacco Smoke Pollution
• Caspase 1

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Antibodies, Neutralizing (pharmacology)
• Apoptosis Regulatory Proteins (metabolism)
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Caspase 1 (metabolism)
• Humans
• Inflammation
• Interleukin-1alpha (antagonists & inhibitors, metabolism)
• Interleukin-1beta (antagonists & inhibitors, metabolism)
• Lung (pathology)
• Macrophages (pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neutrophils (pathology)
• Pulmonary Disease, Chronic Obstructive (etiology, pathology, physiopathology)
• Receptors, Interleukin-1 (metabolism)
• Smoking (adverse effects)
• Tobacco Smoke Pollution (adverse effects)