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The effect of BPIFA1/SPLUNC1 genetic variation on its expression and function in asthmatic airway epithelium
Niccolette Schaefer, … , Sally E. Wenzel, Hong Wei Chu
Niccolette Schaefer, … , Sally E. Wenzel, Hong Wei Chu
Published April 18, 2019
Citation Information: JCI Insight. 2019;4(8):e127237. https://doi.org/10.1172/jci.insight.127237.
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Research Article Inflammation

The effect of BPIFA1/SPLUNC1 genetic variation on its expression and function in asthmatic airway epithelium

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Abstract

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.

Authors

Niccolette Schaefer, Xingnan Li, Max A. Seibold, Nizar N. Jarjour, Loren C. Denlinger, Mario Castro, Andrea M. Coverstone, W. Gerald Teague, Jonathan Boomer, Eugene R. Bleecker, Deborah A. Meyers, Wendy C. Moore, Gregory A. Hawkins, John Fahy, Brenda R. Phillips, David T. Mauger, Azzeddine Dakhama, Shaan Gellatly, Nicole Pavelka, Reena Berman, Y. Peter Di, Sally E. Wenzel, Hong Wei Chu

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Figure 1

Subjects with the rs750064 CC genotype have significantly less BPIFA1 mRNA expression than subjects with the CT and TT genotypes.

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Subjects with the rs750064 CC genotype have significantly less BPIFA1 mR...
BPIFA1 mRNA expression was measured from (A) noncultured nasal epithelial cells of 74 mild to severe subjects with asthma (n = 49 adults, n = 25 children), (B) expanded (submerged culture for 10 days) nasal epithelial cells from 37 asthmatics (n = 33 adults, n = 4 children) without any stimulation, and (C) differentiated (ALI culture for 14 days) mucociliary nasal epithelial cells from subjects with various genotypes (10 CC: 8 White, 2 African American; 8 CT: 8 White, 0 African American; and 4 TT: 4 White, 0 African American) without any stimulation. P values from A represent a linear regression additive genetic model with adjustments for age, sex, and race; B represents a Kruskal-Wallis test; and C represents a Mann-Whitney test. The black line represents the median value.

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