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IL-13 enhances agonist-evoked calcium signals and contractile responses in airway smooth muscle
Authors:Tliba Omar  Deshpande Deepak  Chen Hang  Van Besien Christopher  Kannan Mathur  Panettieri Reynold A  Amrani Yassine
Institution:Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania, BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Abstract:Growing evidence suggests that interleukin (IL)-13, a Th2-type cytokine, plays a critical role in the development of bronchial hyper-responsiveness (BHR), an essential feature of asthma, although the underlying mechanisms remain unknown. In the present study, we investigated whether IL-13 directly affects airway smooth muscle (ASM) function. In murine tracheal rings, IL-13 (100 ng ml-1, 24 h) significantly increased both the carbachol- and KCl-induced maximal force generation without affecting ASM sensitivity. In cultured human ASM cells, IL-13 (50 ng ml-1, 24 h) also augmented cytosolic calcium levels to bradykinin, histamine and carbachol by 60, 35 and 26%, respectively. The present study demonstrates that IL-13 may promote BHR by directly modulating ASM contractility, an effect that may be due to enhanced G protein-coupled receptor (GPCR)-associated calcium signaling.
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