Publication
Title
Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD
Author
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 COPDmouse models. It is unclear whether interleukin (IL)-1 alpha or IL-1 beta, 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-1 alpha or anti-IL-1 beta 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-1 alpha and IL-1 beta 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-1 alpha or IL-1 beta. Interestingly, CS-induced inflammation occurred independently of IL-1 beta activation by the Nlrp3/caspase-1 axis. In human subjects, IL-1 alpha and IL-1 beta 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-1 beta but also IL-1 alpha should be considered as an important mediator in CS-induced inflammation and COPD.
Language
English
Source (journal)
The European respiratory journal / European Respiratory Society [Lausanne] - Copenhagen, 1988, currens
Publication
Copenhagen : 2011
ISSN
0903-1936 [print]
1399-3003 [online]
Volume/pages
38:5(2011), p. 1019-1028
ISI
000296607300006
Full text (Publisher's DOI)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 18.10.2018
Last edited 28.07.2021