一种选择性4型磷酸二酯酶抑制剂T-440可调节Jurkat细胞的细胞内环磷酸腺苷水平和白细胞介素-2的产生。

A selective type 4 phosphodiesterase inhibitor, T-440, modulates intracellular cyclic AMP level and interleukin-2 production of Jurkat cells.

作者信息

Kaminuma O, Mori A, Wada K, Kikkawa H, Ikezawa K, Suko M, Okudaira H

机构信息

Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan.

出版信息

Immunopharmacology. 1998 Jan;38(3):247-52. doi: 10.1016/s0162-3109(97)00071-4.

DOI:10.1016/s0162-3109(97)00071-4

PMID:9506824

Abstract

Effect of a selective type 4 phosphodiesterase (PDE4) inhibitor, T-440, on intracellular cyclic AMP (cAMP) level and interleukin (IL)-2 production of Jurkat cells was investigated. T-440 suppressed both cAMP-PDE activities in cytosolic and membrane fractions of Jurkat cells. Intracellular cAMP level in Jurkat cells was elevated by PGE2 and forskolin but not by T-440. T-440, however, significantly enhanced the increase of cAMP by PGE2. PGE2 and forskolin inhibited IL-2 production of Jurkat cells stimulated with concanavalin A. T-440 by itself did not affect IL-2 production, but significantly enhanced the effect of PGE2 on IL-2 production. The increase of intracellular cAMP by T-440, PGE2, forskolin and T-440 plus PGE2 was well correlated with the inhibition of IL-2 production. These results indicate that IL-2 production of T cells is regulated by cAMP-PDE activity. Immunomodulatory effects of PDE4 inhibitors like T-440 should further be explored in vivo.

摘要

研究了选择性4型磷酸二酯酶（PDE4）抑制剂T-440对Jurkat细胞内环状AMP（cAMP）水平和白细胞介素（IL）-2产生的影响。T-440抑制了Jurkat细胞胞质和膜部分中的cAMP-PDE活性。PGE2和福斯高林可提高Jurkat细胞内的cAMP水平，但T-440不能。然而，T-440显著增强了PGE2引起的cAMP增加。PGE2和福斯高林抑制了伴刀豆球蛋白A刺激的Jurkat细胞的IL-2产生。T-440本身不影响IL-2产生，但显著增强了PGE2对IL-2产生的作用。T-440、PGE2、福斯高林以及T-440加PGE2引起的细胞内cAMP增加与IL-2产生的抑制密切相关。这些结果表明，T细胞的IL-2产生受cAMP-PDE活性调节。像T-440这样的PDE4抑制剂的免疫调节作用应在体内进一步探索。