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

Charity Nofzinger, Valeria Vezzoli, Silvia Dossena, Tony Schönherr, Jan Studnicka, J. Nofzinger, S. Vanoni, S Stephan, Me Silva, Markus Paulmichl, G. Meyer

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

Abstract

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 (N(4) GAS motif) rendered the promoter insensitive to IL-4/IL-13; and that addition of the N(4) GAS motif to an IL-4/IL-13-unresponsive sequence of the human pendrin promoter conferred sensitivity to both ILs.
OriginalspracheEnglisch
Seiten (von - bis)399-405
Seitenumfang7
FachzeitschriftClinical Pharmacology & Therapeutics
Volume90
Issue3
DOIs
PublikationsstatusVeröffentlicht - 2011

Research Field

  • Biosensor Technologies

Schlagwörter

  • ALLERGIC AIRWAYS DISEASE; SYNDROME GENE; FUNCTIONAL-CHARACTERIZATION; SERUM LEVELS; IODIDE TRANSPORT; INTERFERON-GAMMA; BRONCHIAL-ASTHMA; ION-TRANSPORT; WILD-TYPE; IN-VITRO

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