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. The in vivo anti-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.

Promising approaches for the treatment and prevention of viral respiratory illnesses

“…39 Finally, in vitro models have demonstrated that a 1 -antitrypsin exerts anti-inflammatory effects in airway epithelial cells from rhinovirus-infected patients with COPD, potentially through inhibition on caspase-1 activity, suggesting a 1 -antitrypsin as a potential anti-inflammatory agent. 40 extremely narrow. Additional challenges need to be overcome, such as the structural variation of viral proteins, multiple genotypes, and high mutation rates.…”

The Utilization of Alpha-1 Anti-trypsin (A1AT) in Infectious Disease Monitoring and Treatment

“…In turn, A1AT treatment on infected brushed bronchial epithelial cell culture reduces viral load [34]. Moreover, A1AT administration has been proven to suppress the inflammation factors such as IL-8 in infected brushed bronchial epithelial cells and its homolog in mouse, KC (keratinocyte chemoattractant) in wild type C57BL/6 mice [35].…”

“…They also imply administration of A1AT may help A1AT deficient infected patients to counteract the damage caused by the infection. HIV low level in serum precedes HIV infection; deficient patient has higher risk to get infected by HIV [13][14][15][16]; high level in serum but deficient in terms of function predisposes HIV patients with emphysema development [17] inhibits VIRIP to cleave with gp41 [28,29] Rhinovirus no reference available yet inhibits HRV receptor induction [34] and anti inflammatory [35] Dengue virus high level indicates acute phase infection [19;20,21]; higher level in DF and DHF cases compared to healthy control. A trend of higher level as the severity degree increases but not significant [26] no reference available yet…”