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Published ahead of print on February 5, 2004, doi:10.1165/rcmb.2003-0313OC

Am. J. Respir. Cell Mol. Biol., Volume 31, Number 1, July 2004, 36-42

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Submitted on August 21, 2003
Revised on February 5, 2004

Modulation of calcium signaling by IL-13 in human airway smooth muscle: role of CD38/cADPR pathway

Deepak A Deshpande1, Soner Dogan1, Timothy F Walseth2, Steven M Miller3, Yassine Amrani4, Reynold A Panettieri, Jr4, and Mathur S Kannan1*

1 Veterinary PathoBiology, University of Minnesota, Saint Paul, MN, USA, 2 Pharmacology, University of Minnesota, Minneapolis, MN, USA, 3 Physiology, Mayo Clinic, Rochester, MN, USA, 4 Medicine, University of Pennsylvania, Philadelphia, PA, USA

* To whom correspondence should be addressed. E-mail: kanna001{at}umn.edu.

CD38/cyclic-ADP ribose signaling plays an important role in the regulation of intracellular calcium responses to agonists in a variety of cells, including airway smooth muscle cells. The present study was aimed at determining the effect of 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 airway smooth muscle 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 airway smooth muscle cells with IL-13 resulted in increased CD38 expression as determined by RT-PCR, real-time PCR, Western blot analysis and indirect immunofluorescence. Increased CD38 expression was reflected as increased ADP-ribosyl cyclase activity in the airway smooth muscle cell membranes. The net intracellular calcium responses to bradykinin, thrombin, and histamine were significantly (p <= 0.05) higher in cells treated with IL-13 compared to controls. Furthermore, 8-bromo-cADPR, a cADPR antagonist, attenuated IL-13-induced augmented intracellular calcium responses to agonists in human airway smooth muscle cells. These findings indicate that the CD38/cADPR-dependent pathway has a major role in IL-13-induced modulation of calcium signaling in human airway smooth muscle.




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