The effect of BPIFA1/SPLUNC1 genetic variation on its expression and function in asthmatic airway epithelium
Seibold, Max A
Jarjour, Nizar N
Denlinger, Loren C
Coverstone, Andrea M
Teague, W Gerald
Bleecker, Eugene R
Meyers, Deborah A
Moore, Wendy C
Hawkins, Gregory A
Phillips, Brenda R
Mauger, David T
Di, Y Peter
Wenzel, Sally E
Chu, Hong Wei
MetadataShow full item record
PublisherAMER SOC CLINICAL INVESTIGATION INC
CitationSchaefer, 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).
RightsCopyright © 2019 American Society for Clinical Investigation.
Collection InformationThis 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 email@example.com.
AbstractBacterial 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.
VersionFinal published version
SponsorsNIH/NHLBI [R01HL125128, U10HL109257, UL1TR00448, U10HL109168]
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- Authors: Tsou YA, Lin CD, Chen HC, Hsu HY, Wu LT, Chiang-Ni C, Chen CJ, Wu TF, Kao MC, Chen YA, Peng MT, Tsai MH, Chen CM, Lai CH
- Issue date: 2015
- SPLUNC1 deficiency enhances airway eosinophilic inflammation in mice.
- Authors: Thaikoottathil JV, Martin RJ, Di PY, Minor M, Case S, Zhang B, Zhang G, Huang H, Chu HW
- Issue date: 2012 Aug
- Expression of SPLUNC1 protein in nasal polyp epithelial cells in air-liquid interface culture treated with IL-13.
- Authors: Yeh TH, Lee SY, Hsu WC
- Issue date: 2010 Jan-Feb
- IL-27 and type 2 immunity in asthmatic patients: association with severity, CXCL9, and signal transducer and activator of transcription signaling.
- Authors: Xie M, Mustovich AT, Jiang Y, Trudeau JB, Ray A, Ray P, Hu H, Holguin F, Freeman B, Wenzel SE
- Issue date: 2015 Feb
- Identification of BPIFA1/SPLUNC1 as an epithelium-derived smooth muscle relaxing factor.
- Authors: Wu T, Huang J, Moore PJ, Little MS, Walton WG, Fellner RC, Alexis NE, Peter Di Y, Redinbo MR, Tilley SL, Tarran R
- Issue date: 2017 Feb 6