Novel pendrin inhibitor attenuates airway hyperresponsiveness and mucin expression in experimental murine asthma

• Published in: Journal of allergy and clinical immunology Vol. 144; no. 5; pp. 1425 - 1428.e12
• Main Authors: Park, Jinhong, Lee, Hyun Jae, Song, Doona, Gi, Mia, Jo, Sungwoo, Jeon, Dong-kyu, Seo, Yohan, Kim, Bomin, Lee, Ho, Namkung, Wan, Han, Gyoonhee, Choi, Jae Young
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2019; Elsevier Limited
• Subjects: Actin; Asthma; Cystic fibrosis; Gene expression; Inflammation; Lungs; Lysine; Mucin; Poly-L-lysine; Polymerase chain reaction; Protein expression; Respiratory tract; Respiratory tract diseases; Sodium channels; Sodium conductance; Statistical analysis; Thallium; Trinucleotide repeats
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2019.07.016

To the Editor: The transmembrane anion exchanger pendrin (SCL26A4) exchanges Cl− with bases, such as HCO3−, I−, and SCN−, and is the most highly upregulated gene in endobronchial biopsies from patients with asthma.1,2 Interestingly, patients with mutant pendrin have a low prevalence of asthma, and pendrin-null mice show reduced allergic airway inflammation.3-5 These observations indicate that pendrin is a novel target for allergic asthma. The mRNA expression levels and ion channel activities of anoctamin-1, cystic fibrosis transmembrane conductance regulator, and epithelial sodium channels (ENaC) were not altered by long-term treatment with YS-01 (see Fig E3, D-F). YFP fluorescence changes by SCN− influx were monitored using the FLUOstar Omega Microplate Reader (BMG Labtech) and MARS Data Analysis Software (BMG Labtech).Thallium flux assay HEK-293T cells were stably transfected with human ether-a-go-go-related Gene (hERG) and seeded at a density of 7 × 104 cells per well in poly-l-lysine–coated 96-well plate, and the cells were incubated for 48 hours. A value of P less than .05 was considered statistically significant. mRNA Primer sequences PCR product size Pendrin 5′-TTC CCA AAG TGC CAA TCC ATA G-3′ 5′-CCG CAG TGA TCT CAC TCC AAC-3′ 83 bp ANO1 5′-GGA GAA GCA GCA TCT ATT TG-3′ 5′-GAT CTC ATA GAC AAT CGT GC-3′ 82 bp CFTR 5′-AGG AGG CAG TCT GTC CTG AA-3′ 5′-CAC TGC TGG TAT GCT CTC CA-3′ 237 bp ENaCα 5′-CAG CCC ATA CCA GGT CTC AT-3′ 5′-ATG GTG GTG TTG TTG CAG AA-3′ 221 bp ENaCβ 5′-TCC TAC CCT CGT CCC TAC CT-3′ 5′-CCA GGA AGG AGA AAA CCA CA-3′ 151 bp ENaCγ 5′-ACC ACC AGC CAT GGT CTA AG-3′ 5′-GTT CAG GTC CCG GGA TTT AT-3′ 211 bp Duox1 5′-TTC ACG CAG CTC TGT GTC AA-3′ 5′-AGG GAC AGA TCA TAT CCT GGC T-3′ 96 bp Duox2 5′-ACG CAG CTC TGT GTC AAA GGT-3′ 5′-TGA TGA ACG AGA CTC GAC AGC-3′ 90 bp β-Actin 5′-GCA AAG ACC TGT ACG CCA ACA C-3′ 5′-ATC TCC TTC TGC ATC CTG TC-3′ 82 bp Table E1 Primer sequences used for quantitative RT-PCR