Phosphodiesterase 8 (PDE8) regulates chemotaxis of activated lymphocytes

被引：52

作者：

Dong, Hongli ^{[1
]}

Osmanova, Venera ^{[1
]}

Epstein, Paul M. ^{[1
]}

Brocke, Stefan ^{[1
]}

机构：

[1] Univ Connecticut, Ctr Hlth, Dept Pharmacol, Farmington, CT 06030 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2006年 / 345卷 / 02期

关键词：

lymphocyte chemotaxis; cyclic nucleotide phosphodiesterase; CXCL12; cAMP signaling; PDE8; dipyridamole;

D O I：

10.1016/j.bbrc.2006.04.143

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (c) 2006 Elsevier Inc. All rialits reserved.

引用

页码：713 / 719

页数：7

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