IL-13R alpha 2 reverses the effects of IL-13 and IL-4 on bronchial reactivity and acetylcholine-induced Ca2+ signaling

Kellner, Julia; Gamarra, Fernando; Welsch, Ulrich; Joerres, Rudolf A.; Huber, Rudolf M. und Bergner, Albrecht (2007): IL-13R alpha 2 reverses the effects of IL-13 and IL-4 on bronchial reactivity and acetylcholine-induced Ca2+ signaling. In: International Archives of Allergy and Immunology, Nr. 3: S. 199-210

Abstract

Background: The interleukins IL-4 and IL-13 play a key role in the pathophysiology of asthma. The interleukin receptor IL-13R alpha 2 is believed to act as a decoy receptor, but until now, the functional significance of IL-13R alpha 2 remains vague. Methods: Bronchial reactivity was quantified in murine lung slices by digital video microscopy and acetylcholine (ACH)-induced Ca2+ signaling was measured in human airway smooth muscle cells (ASMC) using fluorescence microscopy. Results: IL-4 or IL-13 up to 50 ng/ml induced bronchial hyperreactivity. But after incubation with 100 ng/ml this effect was lost and bronchial responsiveness was again comparable to the control level. The effects of IL-4 and IL-13 on bronchial reactivity were paralleled by the effects on ASMC proliferation. Fifty nanograms per milliliter of IL-4 and IL-13 increased the Ca2+ response of human ASMC to ACH. At 100 ng/ml, however, the effects of the cytokines on the Ca2+ response were no longer evident. The expression of IL-13R alpha 2 increased with increasing concentrations of IL-4 or IL-13, reaching its maximum at 100 ng/ml. Blocking IL-13R alpha 2, the loss of the effect of IL-4 and IL-13 at 100 ng/ml on human ASMC proliferation and the ACH-induced Ca2+ response were no longer present. Conclusions: IL-4 and IL-13 induce bronchial hyperreactivity by changing the Ca2+ homeostasis of ASMC. These effects are counteracted by IL-13R alpha 2. The biological significance of IL-13R alpha 2 might be a protective function by regulating IL-13- and IL-4-mediated signal transduction and thereby limiting pathological alterations in Th2-mediated inflammatory diseases. Copyright (c) 2007 S. Karger AG, Basel.

• Dokumententyp: Zeitschriftenartikel
• Publikationsform: Publisher's Version
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1018-2438
• Allianz-/Nationallizenz: Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
• Sprache: Englisch