Modulation of calcium signaling by interleukin-13 in human airway smooth muscle: Role of CD38/cyclic adenosine diphosphate ribose pathway

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

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

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 responsesto bradykinin, thrombin, and histamine were significantly (P ≤ 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.

Original languageEnglish (US)
Pages (from-to)36-42
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume31
Issue number1
DOIs
StatePublished - Jul 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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