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Publication : Phosphodiesterase 8 (PDE8) regulates chemotaxis of activated lymphocytes.

First Author  Dong H Year  2006
Journal  Biochem Biophys Res Commun Volume  345
Issue  2 Pages  713-9
PubMed ID  16696947 Mgi Jnum  J:109658
Mgi Id  MGI:3629438 Doi  10.1016/j.bbrc.2006.04.143
Citation  Dong H, et al. (2006) Phosphodiesterase 8 (PDE8) regulates chemotaxis of activated lymphocytes. Biochem Biophys Res Commun 345(2):713-9
abstractText  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.
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