Reference : Proinflammatory Cytokines Induce Bronchial Hyperplasia and Squamous Metaplasia in Smoker...
Scientific journals : Article
Human health sciences : Oncology
http://hdl.handle.net/2268/121004
Proinflammatory Cytokines Induce Bronchial Hyperplasia and Squamous Metaplasia in Smokers: Implications for chronic obstructive pulmonary disease therapy.
English
Herfs, Michael mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques]
Hubert, Pascale mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques]
POIRRIER, Anne-Lise [Centre Hospitalier Universitaire de Liège - CHU > > O.R.L.]
Vandevenne [> >]
Renoux, Virginie mailto [Université de Liège - ULg > > > Doct. sc. bioméd. & pharma. (Bologne)]
Habraken, Yvette mailto [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie]
Cataldo, Didier mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path.]
Boniver, Jacques mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques]
Delvenne, Philippe mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques]
2012
American Journal of Respiratory Cell and Molecular Biology
American Thoracic Society
47
1
67-79
Yes (verified by ORBi)
International
1044-1549
1535-4989
New York
NY
[en] Tracheobronchial squamous metaplasia is common in smokers and is associated with both airway obstruction in chronic obstructive pulmonary disease (COPD) and increased risk of lung cancer. Whereas this reversible epithelial replacement is almost always observed in association with chronic inflammation, the role of inflammatory mediators in the pathogenesis of squamous metaplasia is still unclear. In the present study, we investigated the implication of cigarette smoke-mediated pro-inflammatory cytokine up-regulation in the development and treatment of tracheobronchial epithelial hyperplasia and squamous metaplasia. By using immunohistological techniques, we showed a higher epithelial expression of TNFalpha, IL-1beta and IL-6 as well as an activation of NF-kappaB and AP-1/MAPK signalling pathways in the respiratory tract of smoking patients compared to the normal ciliated epithelium of non-smoking patients. In addition, we demonstrated that these signalling pathways strongly influence the proliferation and the differentiation state of in vitro generated normal human airway epithelial basal cells. Finally, we exposed mice to cigarette smoke for 16 weeks and demonstrated that anti-TNFalpha (etanercept), anti-IL-1beta (anakinra) and/or anti-IL-6R (tocilizumab) therapies significantly reduced epithelial hyperplasia and squamous metaplasia development. These data highlight the importance of soluble inflammatory mediators in the pathogenesis of tracheobronchial squamous metaplasia. Therefore, administration of pro-inflammatory cytokine antagonists may have clinical application in the management of COPD patients.
http://hdl.handle.net/2268/121004
10.1165/rcmb.2011-0353OC

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