TY - JOUR
T1 - The effect of BPIFA1/SPLUNC1 genetic variation on its expression and function in asthmatic airway epithelium
AU - Schaefer, Niccolette
AU - Li, Xingnan
AU - Seibold, Max A.
AU - Jarjour, Nizar N.
AU - Denlinger, Loren C.
AU - Castro, Mario
AU - Coverstone, Andrea M.
AU - Teague, W. Gerald
AU - Boomer, Jonathan
AU - Bleecker, Eugene R.
AU - Meyers, Deborah A.
AU - Moore, Wendy C.
AU - Hawkins, Gregory A.
AU - Fahy, John
AU - Phillips, Brenda R.
AU - Mauger, David T.
AU - Dakhama, Azzeddine
AU - Gellatly, Shaan
AU - Pavelka, Nicole
AU - Berman, Reena
AU - Di, Y. Peter
AU - Wenzel, Sally E.
AU - Chu, Hong Wei
N1 - Publisher Copyright:
© 2019 American Society for Clinical Investigation.
PY - 2019
Y1 - 2019
N2 - Bacterial permeability family member A1 (BPIFA1), also known as short palate, lung, and nasal epithelium clone 1 (SPLUNC1), is a protein involved in the antiinflammatory response. The goal of this study was to determine whether BPIFA1 expression in asthmatic airways is regulated by genetic variations, altering epithelial responses to type 2 cytokines (e.g., IL-13). Nasal epithelial cells from patients with mild to severe asthma were collected from the National Heart, Lung, and Blood Institute Severe Asthma Research Program centers, genotyped for rs750064, and measured for BPIFA1. To determine the function of rs750064, cells were cultured at air-liquid interface and treated with IL-13 with or without recombinant human BPIFA1 (rhBPIFA1). Noncultured nasal cells with the rs750064 CC genotype had significantly less BPIFA1 mRNA expression than the CT and TT genotypes. Cultured CC versus CT and TT cells without stimulation maintained less BPIFA1 expression. With IL-13 treatment, CC genotype cells secreted more eotaxin-3 than CT and TT genotype cells. Also, rhBPIFA1 reduced IL-13-mediated eotaxin-3. BPIFA1 mRNA levels negatively correlated with serum IgE and fractional exhaled nitric oxide. Baseline FEV1% levels were lower in the asthma patients with the CC genotype (n = 1,016). Our data suggest that less BPIFA1 in asthma patients with the CC allele may predispose them to greater eosinophilic inflammation, which could be attenuated by rhBPIFA1 protein therapy.
AB - Bacterial permeability family member A1 (BPIFA1), also known as short palate, lung, and nasal epithelium clone 1 (SPLUNC1), is a protein involved in the antiinflammatory response. The goal of this study was to determine whether BPIFA1 expression in asthmatic airways is regulated by genetic variations, altering epithelial responses to type 2 cytokines (e.g., IL-13). Nasal epithelial cells from patients with mild to severe asthma were collected from the National Heart, Lung, and Blood Institute Severe Asthma Research Program centers, genotyped for rs750064, and measured for BPIFA1. To determine the function of rs750064, cells were cultured at air-liquid interface and treated with IL-13 with or without recombinant human BPIFA1 (rhBPIFA1). Noncultured nasal cells with the rs750064 CC genotype had significantly less BPIFA1 mRNA expression than the CT and TT genotypes. Cultured CC versus CT and TT cells without stimulation maintained less BPIFA1 expression. With IL-13 treatment, CC genotype cells secreted more eotaxin-3 than CT and TT genotype cells. Also, rhBPIFA1 reduced IL-13-mediated eotaxin-3. BPIFA1 mRNA levels negatively correlated with serum IgE and fractional exhaled nitric oxide. Baseline FEV1% levels were lower in the asthma patients with the CC genotype (n = 1,016). Our data suggest that less BPIFA1 in asthma patients with the CC allele may predispose them to greater eosinophilic inflammation, which could be attenuated by rhBPIFA1 protein therapy.
UR - http://www.scopus.com/inward/record.url?scp=85070658290&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.127237
DO - 10.1172/jci.insight.127237
M3 - Article
C2 - 30996135
AN - SCOPUS:85070658290
VL - 4
JO - JCI insight
JF - JCI insight
SN - 2379-3708
IS - 8
M1 - e127237
ER -