TY - JOUR T1 - Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/09031936.00158110 SP - erj01581-2010 AU - N.S. Pauwels AU - K.R. Bracke AU - L.L. Dupont AU - G.R. Van Pottelberge AU - S. Provoost AU - T.V Berghe AU - P. Vandenabeele AU - B.N. Lambrecht AU - G.F. Joos AU - G.G. Brusselle Y1 - 2011/05/26 UR - http://erj.ersjournals.com/content/early/2011/05/26/09031936.00158110.abstract N2 - Cigarette smoke (CS), the primary risk factor of COPD, leads to pulmonary inflammation through IL-1Receptor-I (IL-1RI) signalling, as determined using COPD mouse models. It is unclear whether 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 KO, Nlrp3 KO and caspase-1 KO mice to CS for 3 days or 4 weeks and evaluated pulmonary inflammation. Additionaly, 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 neutralizing IL-1α or IL-1β. Interestingly, CS-induced inflammation occured independent from IL-1β activation by the Nlrp3/caspase-1 axis. In human subjects, IL-1α and IL-1β were significantly increased, respectively in total lung tissue and induced sputum of patients with COPD, compared to 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. ER -