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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 T; Dakhama, Azzeddine; Gellatly, Shaan; Pavelka, Nicole; Berman, Reena; Di, Y Peter; Wenzel, Sally E; Chu, Hong Wei.
Afiliación
  • Schaefer N; National Jewish Health, Denver, Colorado, USA.
  • Li X; University of Arizona, Tucson, Arizona, USA.
  • Seibold MA; National Jewish Health, Denver, Colorado, USA.
  • Jarjour NN; University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • Denlinger LC; University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • Castro M; Washington University in St. Louis, St. Louis, Missouri, USA.
  • Coverstone AM; Washington University in St. Louis, St. Louis, Missouri, USA.
  • Teague WG; University of Virginia, Charlottesville, Virginia, USA.
  • Boomer J; Washington University in St. Louis, St. Louis, Missouri, USA.
  • Bleecker ER; University of Arizona, Tucson, Arizona, USA.
  • Meyers DA; University of Arizona, Tucson, Arizona, USA.
  • Moore WC; Wake Forest University, Winston-Salem, North Carolina, USA.
  • Hawkins GA; Wake Forest University, Winston-Salem, North Carolina, USA.
  • Fahy J; UCSF, San Francisco, California, USA.
  • Phillips BR; UCSF, San Francisco, California, USA.
  • Mauger DT; Pennsylvania State University, Centre County, Pennsylvania, USA.
  • Dakhama A; National Jewish Health, Denver, Colorado, USA.
  • Gellatly S; National Jewish Health, Denver, Colorado, USA.
  • Pavelka N; National Jewish Health, Denver, Colorado, USA.
  • Berman R; National Jewish Health, Denver, Colorado, USA.
  • Di YP; University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Wenzel SE; University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Chu HW; National Jewish Health, Denver, Colorado, USA.
JCI Insight ; 4(8)2019 04 18.
Article en En | MEDLINE | ID: mdl-30996135
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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fosfoproteínas / Asma / Glicoproteínas / Transducción de Señal / Regulación de la Expresión Génica / Células Epiteliales Tipo de estudio: Diagnostic_studies Idioma: En Revista: JCI Insight Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fosfoproteínas / Asma / Glicoproteínas / Transducción de Señal / Regulación de la Expresión Génica / Células Epiteliales Tipo de estudio: Diagnostic_studies Idioma: En Revista: JCI Insight Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos