title: The Anti-inflammatory Effect of Alpha-1 Antitrypsin in Rhinovirus-infected Human Airway Epithelial Cells.
abstract: OBJECTIVE
  Excessive airway inflammation is seen in chronic obstructive pulmonary disease (COPD) patients experiencing acute exacerbations, which are often associated with human rhinovirus (HRV) infection. Alpha-1 antitrypsin (A1AT) has anti-inflammatory function in endothelial cells and monocytes, but its anti-inflammatory effect has not been investigated in COPD airway epithelial cells. We determined A1AT's anti-inflammatory function in COPD airway epithelial cells and the underlying mechanisms such as the role of caspase-1.
  
  
  METHODS
  Brushed bronchial epithelial cells from COPD and normal subjects were cultured at air-liquid interface and treated with A1AT or bovine serum albumin (BSA, control) two hours prior to whole cigarette smoke (WCS) or air exposure, followed by HRV-16 infection. After 24 hours of viral infection, cell supernatants were collected for measuring IL-8, and cells were examined for caspase-1. Thein vivoanti-inflammatory function of A1AT was determined by infecting mice intranasally with HRV-1B followed by aerosolized A1AT or BSA.
  
  
  RESULTS
  A1AT significantly reduced WCS and HRV-16-induced IL-8 production in normal and COPD airway epithelial cells. COPD cells are less sensitive to A1AT's anti-inflammatory effect than normal cells. A1AT exerted the anti-inflammatory function in part via reducing caspase-1 in normal cells, but not in COPD cells. In mice, A1AT significantly reduced HRV-1B induced lung neutrophilic inflammation.
  
  
  CONCLUSIONS
  A1AT exerts an anti-inflammatory effect in cigarette smoke-exposed and HRV-infected human airway epithelial cells, which may be related to its inhibitory effect on caspase-1 activity.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Reena
authors.initials: R
authors.lastname: Berman
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Connor
authors.initials: C
authors.lastname: Stevenson
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA; Department of Immunology and Microbiology, University of Colorado Denver School of Medicine, Aurora, CO, USA.
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
keywords: Airway epithelial cell; Alpha-1 antitrypsin; COPD; Cigarette smoke; Rhinovirus