STAT6 Links IL‐4/IL‐13 Stimulation With Pendrin Expression in Asthma and Chronic Obstructive Pulmonary Disease

• Published in: Clinical pharmacology and therapeutics 2011-09, Vol.90 (3), p.399-405
• Main Authors: Nofziger, C, Vezzoli, V, Dossena, S, Schönherr, T, Studnicka, J, Nofziger, J, Vanoni, S, Stephan, S, Silva, M E, Meyer, G, Paulmichl, M
• Format: Article
• Language: English
• Subjects: Asthma - genetics; Asthma - physiopathology; Base Pairing; Binding Sites; Biological and medical sciences; Cell Line; Chronic obstructive pulmonary disease, asthma; Epithelial Cells - metabolism; Epithelial Cells - pathology; Gene Expression Regulation; Humans; Interleukin-13 - genetics; Interleukin-13 - metabolism; Interleukin-4 - genetics; Interleukin-4 - metabolism; Kidney; Lung - metabolism; Lung - pathology; Lung - physiopathology; Medical sciences; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Molecular Sequence Data; Molecular Targeted Therapy; Mucus - metabolism; Mutation; Pharmacology. Drug treatments; Pneumology; Promoter Regions, Genetic; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - physiopathology; Respiratory System - metabolism; Respiratory System - pathology; Respiratory System - physiopathology; Signal Transduction; STAT6 Transcription Factor - metabolism
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1038/clpt.2011.128

Signaling through the interleukin‐4/interleukin‐13 (IL‐4/IL‐13) receptor complex is a crucial mechanism in the development of bronchial asthma and chronic obstructive pulmonary disease (COPD). In bronchial epithelial cells, this signaling pathway leads to changes in the expression levels of several genes that are possibly involved in protection against and/or pathogenesis of these diseases. The expression of pendrin (SLC26A4), a candidate for the latter category, is upregulated by IL‐4/IL‐13 and leads to overproduction of mucus and increased viscosity of the airway surface liquid (ASL). Therefore, elucidating the transcriptional regulation of pendrin could aid in the development of new pharmacological leads for asthma and/or COPD therapy. Here we show that IL‐4/IL‐13 significantly increased human pendrin promoter activity in HEK‐Blue cells but not in STAT6‐deficient HEK293 Phoenix cells; that mutation of the STAT6 binding site (N4 GAS motif) rendered the promoter insensitive to IL‐4/IL‐13; and that addition of the N4 GAS motif to an IL‐4/IL‐13‐unresponsive sequence of the human pendrin promoter conferred sensitivity to both ILs. Clinical Pharmacology & Therapeutics (2011) 90 3, 399–405. doi:10.1038/clpt.2011.128