The effect of BPIFA1/SPLUNC1 genetic variation on its expression and function in asthmatic airway epithelium
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Schaefer, NiccoletteLi, Xingnan
Seibold, Max A
Jarjour, Nizar N
Denlinger, Loren C
Castro, Mario
Coverstone, Andrea M
Teague, W Gerald
Boomer, Jonathan
Bleecker, Eugene R
Meyers, Deborah A
Moore, Wendy C
Hawkins, Gregory A
Fahy, John
Phillips, Brenda R
Mauger, David T
Dakhama, Azzeddine
Gellatly, Shaan
Pavelka, Nicole
Berman, Reena
Di, Y Peter
Wenzel, Sally E
Chu, Hong Wei
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Univ ArizonaIssue Date
2019-04-18
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AMER SOC CLINICAL INVESTIGATION INCCitation
Schaefer, N., Li, X., Seibold, M. A., Jarjour, N. N., Denlinger, L. C., Castro, M., ... & Meyers, D. A. (2019). The effect of BPIFA1/SPLUNC1 genetic variation on its expression and function in asthmatic airway epithelium. JCI insight, 4(8).Journal
JCI INSIGHTRights
Copyright © 2019 American Society for Clinical Investigation.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.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 11-13 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.EISSN
2379-3708PubMed ID
30996135Version
Final published versionSponsors
NIH/NHLBI [R01HL125128, U10HL109257, UL1TR00448, U10HL109168]ae974a485f413a2113503eed53cd6c53
10.1172/jci.insight.127237
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