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

NS Pauwels, Ken Bracke (UGent) , Lisa Dupont (UGent) , Geert Van Pottelberge, Sharen Provoost (UGent) , Tom Vanden Berghe (UGent) , Peter Vandenabeele (UGent) , Bart Lambrecht (UGent) , Guy Joos (UGent) and Guy Brusselle (UGent)
(2011) EUROPEAN RESPIRATORY JOURNAL. 38(5). p.1019-1028
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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.
Keywords
cigarette smoke, inflammasome, chronic obstructive pulmonary disease, Caspase-1, interleukin-1, Nlrp3, DENDRITIC CELLS, DYING CELLS, MICE, INTERLEUKIN-1-BETA, CASPASE-1, IMMUNITY, DISEASE, FAMILY

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Chicago
Pauwels, NS, Ken Bracke, Lisa Dupont, Geert Van Pottelberge, Sharen Provoost, Tom Vanden Berghe, Peter Vandenabeele, Bart Lambrecht, Guy Joos, and Guy Brusselle. 2011. “Role of IL-1α and the Nlrp3/caspase-1/IL-1β Axis in Cigarette Smoke-induced Pulmonary Inflammation and COPD.” European Respiratory Journal 38 (5): 1019–1028.
APA
Pauwels, NS, Bracke, K., Dupont, L., Van Pottelberge, G., Provoost, S., Vanden Berghe, T., Vandenabeele, P., et al. (2011). Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD. EUROPEAN RESPIRATORY JOURNAL, 38(5), 1019–1028.
Vancouver
1.
Pauwels N, Bracke K, Dupont L, Van Pottelberge G, Provoost S, Vanden Berghe T, et al. Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD. EUROPEAN RESPIRATORY JOURNAL. 2011;38(5):1019–28.
MLA
Pauwels, NS, Ken Bracke, Lisa Dupont, et al. “Role of IL-1α and the Nlrp3/caspase-1/IL-1β Axis in Cigarette Smoke-induced Pulmonary Inflammation and COPD.” EUROPEAN RESPIRATORY JOURNAL 38.5 (2011): 1019–1028. Print.
@article{1964008,
  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.},
  author       = {Pauwels, NS and Bracke, Ken and Dupont, Lisa and Van Pottelberge, Geert and Provoost, Sharen and Vanden Berghe, Tom and Vandenabeele, Peter and Lambrecht, Bart and Joos, Guy and Brusselle, Guy},
  issn         = {0903-1936},
  journal      = {EUROPEAN RESPIRATORY JOURNAL},
  keyword      = {cigarette smoke,inflammasome,chronic obstructive pulmonary disease,Caspase-1,interleukin-1,Nlrp3,DENDRITIC CELLS,DYING CELLS,MICE,INTERLEUKIN-1-BETA,CASPASE-1,IMMUNITY,DISEASE,FAMILY},
  language     = {eng},
  number       = {5},
  pages        = {1019--1028},
  title        = {Role of IL-1\ensuremath{\alpha} and the Nlrp3/caspase-1/IL-1\ensuremath{\beta} axis in cigarette smoke-induced pulmonary inflammation and COPD},
  url          = {http://dx.doi.org/10.1183/09031936.00158110},
  volume       = {38},
  year         = {2011},
}

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