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

Autor: Azzeddine Dakhama, Max A. Seibold, Deborah A. Meyers, Loren C. Denlinger, Niccolette Schaefer, Brenda R. Phillips, John V. Fahy, Wendy C. Moore, Nizar N. Jarjour, Shaan L. Gellatly, David T. Mauger, Reena Berman, Mario Castro, Nicole Pavelka, W. Gerald Teague, Jonathan S. Boomer, Gregory A. Hawkins, Hong Wei Chu, Sally E. Wenzel, Y. Peter Di, Xingnan Li, Eugene R. Bleecker, Andrea M. Coverstone
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Clone (cell biology)
Stimulation
Severity of Illness Index
0302 clinical medicine
Forced Expiratory Volume
Genotype
2.1 Biological and endogenous factors
Aetiology
Child
Lung
Cells
Cultured
Cultured
Interleukin-13
General Medicine
Single Nucleotide
Middle Aged
Recombinant Proteins
Th2 response
medicine.anatomical_structure
030220 oncology & carcinogenesis
Respiratory
Female
medicine.symptom
Research Article
Signal Transduction
Adult
Adolescent
Cells
Primary Cell Culture
Inflammation
Polymorphism
Single Nucleotide
03 medical and health sciences
Clinical Research
medicine
Genetics
Humans
Genetic Predisposition to Disease
Polymorphism
Alleles
Asthma
Glycoproteins
Aged
business.industry
Chemokine CCL26
Epithelial Cells
medicine.disease
Phosphoproteins
Epithelium
Eosinophils
Nasal Mucosa
030104 developmental biology
Gene Expression Regulation
Exhaled nitric oxide
Immunology
business
Zdroj: JCI insight, vol 4, iss 8
Popis: 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.
Databáze: OpenAIRE
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