Details

Autor(en) / Beteiligte

• Deshpande, Deepak A
• Dogan, Soner
• Walseth, Timothy F
• Miller, Steven M
• Amrani, Yassine
• Panettieri, Reynold A
• Kannan, Mathur S

Titel

Modulation of Calcium Signaling by Interleukin-13 in Human Airway Smooth Muscle: Role of CD38/Cyclic Adenosine Diphosphate Ribose Pathway

Ist Teil von

• American journal of respiratory cell and molecular biology, 2004-07, Vol.31 (1), p.36-42

Ort / Verlag

United States: Am Thoracic Soc

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.