Abstract
CD38/cyclic adenosine diphosphate ribose (cADPR) signaling plays an important role in the regulation of intracellular calcium responses to agonists in a variety of cells, including airway smooth muscle (ASM) cells. The present study was aimed at determining the effect of interleukin (IL)-13, a cytokine implicated in the pathogenesis of asthma, on CD38/cADPR signaling and to ascertain the contribution of CD38/cADPR signaling to IL-13-induced airway hyperresponsiveness. Human ASM cells maintained in culture were exposed to 50 ng/ml IL-13 for 22 h and levels of CD38 expression and intracellular calcium responses to agonists were measured. Treatment of human ASM cells with IL-13 resulted in increased CD38 expression as determined by real-time polymerase chain reaction, Western blot analysis, and indirect immunofluorescence. Increased CD38 expression was reflected as increased ADP-ribosyl cyclase activity in the ASM cell membranes. The net intracellular calcium responses to bradykinin, thrombin, and histamine were significantly (P < or = 0.05) higher in cells treated with IL-13 compared with controls. Furthermore, 8-bromo-cADPR, a cADPR antagonist, attenuated IL-13-induced augmented intracellular calcium responses to agonists in human ASM cells. These findings indicate that the CD38/cADPR-dependent pathway has a major role in IL-13-induced modulation of calcium signaling in human ASM.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ADP-ribosyl Cyclase / immunology
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ADP-ribosyl Cyclase / physiology*
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ADP-ribosyl Cyclase 1
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Antigens, CD / immunology
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Antigens, CD / physiology*
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Asthma / immunology
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Asthma / metabolism
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Asthma / physiopathology
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Bronchi / immunology
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Bronchi / metabolism*
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Bronchi / physiopathology
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Bronchial Hyperreactivity / immunology
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Bronchial Hyperreactivity / metabolism
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Bronchial Hyperreactivity / physiopathology
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Bronchoconstriction / drug effects
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Bronchoconstriction / physiology
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Bronchoconstrictor Agents / pharmacology
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Calcium / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / immunology*
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Cell Membrane / drug effects
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Cells, Cultured
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Cyclic ADP-Ribose / analogs & derivatives
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Cyclic ADP-Ribose / antagonists & inhibitors
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Cyclic ADP-Ribose / metabolism
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Cyclic ADP-Ribose / pharmacology
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Humans
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Interleukin-13 / immunology
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Interleukin-13 / metabolism*
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Interleukin-13 / pharmacology
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Intracellular Fluid / drug effects
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Intracellular Fluid / metabolism
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Membrane Glycoproteins
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Muscle, Smooth / immunology
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Muscle, Smooth / metabolism*
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Muscle, Smooth / physiopathology
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Myocytes, Smooth Muscle / drug effects
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Myocytes, Smooth Muscle / immunology
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Myocytes, Smooth Muscle / metabolism*
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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Antigens, CD
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Bronchoconstrictor Agents
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Interleukin-13
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Membrane Glycoproteins
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Cyclic ADP-Ribose
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ADP-ribosyl Cyclase
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CD38 protein, human
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ADP-ribosyl Cyclase 1
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Calcium