Modulation of human airway smooth muscle proliferation by type 3 phosphodiesterase inhibition.

نویسندگان

  • Charlotte K Billington
  • Sunil K Joseph
  • Caroline Swan
  • Mark G H Scott
  • Timothy M Jobson
  • Ian P Hall
چکیده

Elevation in cell cAMP content can inhibit mitogenic signaling in cultured human airway smooth muscle (HASM) cells. We studied the effects of the type 3-selective phosphodiesterase inhibitor siguazodan, the type 4-selective phosphodiesterase inhibitor rolipram, and the nonselective inhibitor 3-isobutyl-1-methylxanthine (IBMX) on proliferation of cultured HASM cells. At concentrations selective for the type 3 phosphodiesterase isoform, siguazodan inhibited both [3H]thymidine incorporation (IC50 2 μM) and the increase in cell number (10 μM; 64% reduction) induced by platelet-derived growth factor-BB (20 ng/ml). These effects were mimicked by IBMX. At concentrations selective for type 4 phosphodiesterase inhibition, rolipram was without effect. A 20-min exposure to siguazodan and rolipram did not increase whole cell cAMP levels. However, in HASM cells transfected with a cAMP-responsive luciferase reporter (p6CRE/Luc), increases in cAMP-driven luciferase expression were seen with siguazodan (3.9-fold) and IBMX (16.5-fold). These data suggest that inhibition of the type 3 phosphodiesterase isoform present in airway smooth muscle results in inhibition of mitogenic signaling, possibly through an increase in cAMP-driven gene expression.

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ALUNG Mar. 20/3

Billington, Charlotte K., Sunil K. Joseph, Caroline Swan, Mark G. H. Scott, Timothy M. Jobson, and Ian P. Hall. Modulation of human airway smooth muscle proliferation by type 3 phosphodiesterase inhibition. Am. J. Physiol. 276 (Lung Cell. Mol. Physiol. 20): L412–L419, 1999.— Elevation in cell cAMP content can inhibit mitogenic signaling in cultured human airway smooth muscle (HASM) cells. We st...

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عنوان ژورنال:
  • The American journal of physiology

دوره 276 3 Pt 1  شماره 

صفحات  -

تاریخ انتشار 1999