Proinflammatory Cytokines Induce Bronchial Hyperplasia and Squamous Metaplasia in Smokers
| Autor: | Yvette Habraken, Didier Cataldo, Michael Herfs, Pascale Hubert, Virginie Renoux, Anne-Lise Poirrier, Patricia Vandevenne, Jacques Boniver, Philippe Delvenne |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty MAP Kinase Signaling System Neutrophils Interleukin-1beta Clinical Biochemistry Bronchi Inflammation Antibodies Monoclonal Humanized Receptors Tumor Necrosis Factor Etanercept Proinflammatory cytokine Pathogenesis Mice Pulmonary Disease Chronic Obstructive Smoke Metaplasia medicine Animals Humans Molecular Biology Cells Cultured COPD Hyperplasia Interleukin-6 Tumor Necrosis Factor-alpha business.industry Smoking NF-kappa B Cell Biology medicine.disease Receptors Interleukin-6 Squamous metaplasia Mice Inbred C57BL Transcription Factor AP-1 Interleukin 1 Receptor Antagonist Protein medicine.anatomical_structure Immunoglobulin G Immunology Cytokines medicine.symptom business Respiratory tract |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 47:67-79 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/rcmb.2011-0353oc |
| Popis: | 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. Although this reversible epithelial replacement is almost always observed in association with chronic inflammation, the role of inflammatory mediators in the pathogenesis of squamous metaplasia remains unclear. In the present study, we investigated the implication of cigarette smoke-mediated proinflammatory cytokine up-regulation in the development and treatment of tracheobronchial epithelial hyperplasia and squamous metaplasia. Using immunohistological techniques, we showed a higher epithelial expression of TNF-α, IL-1β, and IL-6, as well as an activation of NF-κB and activator protein-1/mitogen-activated protein kinase signaling pathways in the respiratory tract of smoking patients, compared with the normal ciliated epithelium of nonsmoking patients. In addition, we demonstrated that these signaling pathways strongly influence the proliferation and 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-TNF-α (etanercept), anti-IL-1β (anakinra), and/or anti-IL-6R (tocilizumab) therapies significantly reduced epithelial hyperplasia and the development of squamous metaplasia. These data highlight the importance of soluble inflammatory mediators in the pathogenesis of tracheobronchial squamous metaplasia. Therefore, the administration of proinflammatory cytokine antagonists may have clinical applications in the management of patients with COPD. |
| Databáze: | OpenAIRE |
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