title: Tumor necrosis factor-α driven inflammation in alpha-1 antitrypsin deficiency: a new model of pathogenesis and treatment.
abstract: Alpha-1 antitrypsin (AAT) deficiency (AATD) has traditionally been thought of as a genetic disorder characterized by lung destruction and early emphysema in a low AAT, and high neutrophil elastase (NE) environment in the lungs of affected individuals. Recently, a growing body of evidence has emerged to support the hypothesis that tumor necrosis factor alpha (TNF-α) is essential in the pathogenesis of both genetic AATD and non-genetic chronic obstructive pulmonary disease (COPD). Reports have highlighted the importance of TNF-α driven immune cell dysfunction in the development of lung disease in AATD. The authors discuss the role of AAT as a key modulator of TNF-α signaling firstly in the setting of AATD and secondly in other conditions where AAT augmentation therapy has potential utility as a novel therapy.
authors.affiliation: a Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre , Beaumont Hospital , Dublin , Ireland.
authors.forename: Killian
authors.initials: K
authors.lastname: Hurley
authors.affiliation: a Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre , Beaumont Hospital , Dublin , Ireland.
authors.forename: Emer P
authors.initials: EP
authors.lastname: Reeves
authors.affiliation: a Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre , Beaumont Hospital , Dublin , Ireland.
authors.forename: Tomás P
authors.initials: TP
authors.lastname: Carroll
authors.affiliation: a Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre , Beaumont Hospital , Dublin , Ireland.
authors.forename: Noel G
authors.initials: NG
authors.lastname: McElvaney
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency / Q000503:physiopathology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000515:alpha 1-Antitrypsin
keywords: ADAM-17; Alpha-1 antitrypsin; TNF-α; alpha-1 antitrypsin augmentation therapy; alpha-1 antitrypsin deficiency; chronic obstructive pulmonary disease; inflammation; neutrophils