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

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 Mauger, Azzeddine Dakhama, Shaan Gellatly, Nicole Pavelka, Reena Berman & 3 others Y. Peter Di, Sally E. Wenzel, Hong Wei Chu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere127237
JournalJCI Insight
Volume4
Issue number8
DOIs
StatePublished - Jan 1 2019

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Nasal Mucosa
Palate
Permeability
Epithelium
Clone Cells
Lung
Interleukin-13
Genotype
Asthma
Nose
National Heart, Lung, and Blood Institute (U.S.)
Messenger RNA
Immunoglobulin E
Cultured Cells
Nitric Oxide
Anti-Inflammatory Agents
Epithelial Cells
Alleles
Air
Cytokines

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Schaefer, N., Li, X., Seibold, M. A., Jarjour, N. N., Denlinger, L. C., Castro, M., ... Chu, H. W. (2019). The effect of BPIFA1/SPLUNC1 genetic variation on its expression and function in asthmatic airway epithelium. JCI Insight, 4(8), [e127237]. https://doi.org/10.1172/jci.insight.127237
Schaefer, Niccolette ; Li, 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 ; Dakhama, Azzeddine ; Gellatly, Shaan ; Pavelka, Nicole ; Berman, Reena ; Di, Y. Peter ; Wenzel, Sally E. ; Chu, Hong Wei. / The effect of BPIFA1/SPLUNC1 genetic variation on its expression and function in asthmatic airway epithelium. In: JCI Insight. 2019 ; Vol. 4, No. 8.
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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.",
author = "Niccolette Schaefer and Xingnan Li and Seibold, {Max A.} and Jarjour, {Nizar N.} and Denlinger, {Loren C.} and Mario Castro and Coverstone, {Andrea M.} and Teague, {W. Gerald} and Jonathan Boomer and Bleecker, {Eugene R.} and Meyers, {Deborah A.} and Moore, {Wendy C.} and Hawkins, {Gregory A.} and John Fahy and Phillips, {Brenda R.} and David Mauger and Azzeddine Dakhama and Shaan Gellatly and Nicole Pavelka and Reena Berman and Di, {Y. Peter} and Wenzel, {Sally E.} and Chu, {Hong Wei}",
year = "2019",
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doi = "10.1172/jci.insight.127237",
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Schaefer, N, Li, X, Seibold, MA, Jarjour, NN, Denlinger, LC, Castro, M, Coverstone, AM, Teague, WG, Boomer, J, Bleecker, ER, Meyers, DA, Moore, WC, Hawkins, GA, Fahy, J, Phillips, BR, Mauger, D, Dakhama, A, Gellatly, S, Pavelka, N, Berman, R, Di, YP, Wenzel, SE & Chu, HW 2019, 'The effect of BPIFA1/SPLUNC1 genetic variation on its expression and function in asthmatic airway epithelium', JCI Insight, vol. 4, no. 8, e127237. https://doi.org/10.1172/jci.insight.127237

The effect of BPIFA1/SPLUNC1 genetic variation on its expression and function in asthmatic airway epithelium. / Schaefer, Niccolette; Li, 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; Dakhama, Azzeddine; Gellatly, Shaan; Pavelka, Nicole; Berman, Reena; Di, Y. Peter; Wenzel, Sally E.; Chu, Hong Wei.

In: JCI Insight, Vol. 4, No. 8, e127237, 01.01.2019.

Research output: Contribution to journalArticle

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

AU - Dakhama, Azzeddine

AU - Gellatly, Shaan

AU - Pavelka, Nicole

AU - Berman, Reena

AU - Di, Y. Peter

AU - Wenzel, Sally E.

AU - Chu, Hong Wei

PY - 2019/1/1

Y1 - 2019/1/1

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.

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DO - 10.1172/jci.insight.127237

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