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

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.