Phosphodiesterase 8 (PDE8) regulates chemotaxis of activated lymphocytes

Biochem Biophys Res Commun. 2006 Jun 30;345(2):713-9. doi: 10.1016/j.bbrc.2006.04.143. Epub 2006 May 3.


The immune system depends on chemokines to recruit lymphocytes to tissues in inflammatory diseases. This study identifies PDE8 as a new target for inhibition of chemotaxis of activated lymphocytes. Chemotactic responses of unstimulated and concanavalin A-stimulated mouse splenocytes and their modulation by agents that stimulate the cAMP signaling pathway were compared. Dibutyryl cAMP inhibited migration of both cell types. In contrast, forskolin and 3-isobutyl-1-methylxanthine each inhibited migration of unstimulated splenocytes, with little effect on migration of stimulated splenocytes. Only dipyridamole alone, a PDE inhibitor capable of inhibiting PDE8, strongly inhibited migration of stimulated and unstimulated splenocytes and this inhibition was enhanced by forskolin and reversed by a PKA antagonist. Following concanavalin A stimulation, mRNA for PDE8A1 was induced. These results suggest that in employing PDE inhibitor therapy for inflammatory illnesses, inhibition of PDE8 may be required to inhibit migration of activated lymphocytes to achieve a full therapeutic effect.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
  • 3',5'-Cyclic-AMP Phosphodiesterases / physiology*
  • Animals
  • Chemotaxis / drug effects
  • Chemotaxis / physiology*
  • Colforsin / pharmacology
  • Concanavalin A / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dipyridamole / pharmacology
  • Inflammation / drug therapy
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / physiology*
  • Mice
  • Phosphodiesterase Inhibitors / pharmacology
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / metabolism
  • Time Factors


  • Phosphodiesterase Inhibitors
  • RNA, Messenger
  • Concanavalin A
  • Colforsin
  • Dipyridamole
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Pde8a protein, mouse
  • 1-Methyl-3-isobutylxanthine