IL-13 enhances agonist-evoked calcium signals and contractile responses in airway smooth muscle.
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.
Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania, BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Omar
O
Tliba
Deepak
D
Deshpande
Hang
H
Chen
Christopher
C
Van Besien
Mathur
M
Kannan
Reynold A
RA
Panettieri
Yassine
Y
Amrani
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*
D018793:Interleukin-13; D011994:Recombinant Proteins; D011189:Potassium Chloride; D006632:Histamine; D002217:Carbachol; D001920:Bradykinin; D002118:Calcium