title: Immune and genetic mechanisms in COPD: possible targets for therapeutic interventions.
abstract: Genetic, immune and environmental interactions are key elements for the development of COPD. Cigarette smoking is considered the primary risk factor initiating inflammatory cascades in genetically susceptible individuals. The "danger signals" elicited by the injured cells of non-specific immunity induce the downstream activation of proinflammatory cascades and antigen-specific adaptive immune responses. The produced oxidative stress further damages the lung leading to acquired genetic changes (histone deacetylation, microsatellite DNA instability, DNA methylation, telomere shortening, miRNA alterations) due to an inefficient DNA repair machinery. On the other hand, augmented apoptosis, impaired efferocytosis and abnormal tissue remodeling contribute to the chronic inflammatory response and tissue destruction in COPD. This review focuses on the role of genetic, epigenetic and immune mechanisms in the development of COPD in order to put forward possible prognostic and therapeutic targets.
authors.affiliation: Department of Thoracic Medicine, University Hospital of Heraklion & Medical School, University of Crete, 71110 Heraklion, Crete, Greece. tzortzaki@med.uoc.gr
authors.forename: Eleni G
authors.initials: EG
authors.lastname: Tzortzaki
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
authors.forename: Eirini
authors.initials: E
authors.lastname: Neofytou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Soulitzis
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Siafakas
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017209:Apoptosis; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects