Modulation of calcium signaling by interleukin-13 in human airway smooth muscle: role of CD38/cyclic adenosine diphosphate ribose pathway.
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.
Deshpande
Deepak A
DA
Department of Veterinary PathoBiology, University of Minnesota, St. Paul, MN, USA.
Dogan
Soner
S
Walseth
Timothy F
TF
Miller
Steven M
SM
Amrani
Yassine
Y
Panettieri
Reynold A
RA
Kannan
Mathur S
MS
D036541:ADP-ribosyl Cyclase / Q000276:immunology / Q000502:physiology*; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001980:Bronchi / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology*; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins; D009130:Muscle, Smooth / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D015703:Antigens, CD; D016085:Bronchoconstrictor Agents; D018793:Interleukin-13; D008562:Membrane Glycoproteins; D036563:Cyclic ADP-Ribose; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium