Wang P, Wu P, Ohleth K M, Egan R W, Billah M M
Allergy Department, Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
Mol Pharmacol. 1999 Jul;56(1):170-4. doi: 10.1124/mol.56.1.170.
The type 4 phosphodiesterase (PDE4) is the predominant PDE isozyme in various leukocytes and plays a key role in the regulation of inflammatory cell activation. There are four PDE4 subtypes (A, B, C, and D), and within each subtype, there are multiple variants. Very recently, we found in monocytes that PDE4B gene expression is selectively induced by lipopolysaccharide (LPS) and that the induction is inhibited by interleukin (IL)-10 and IL-4. In this study, we show that the PDE4B gene is constitutively expressed in neutrophils and that this expression remains unaffected by LPS or IL-10. PDE4B is the predominant subtype in neutrophils and in unstimulated or LPS-stimulated monocytes, and in these cells, the PDE4B2 variant is the only detectable molecular species of PDE4B. Therefore, PDE4B2 is the predominant PDE isoform in human neutrophils and monocytes, and its expression is regulated differently by these two cell types. Furthermore, leukocytes are the most dominant source of PDE4B2, suggesting that PDE4B2 is a relatively specific target for discovering anti-inflammatory drugs.
4型磷酸二酯酶（PDE4）是各种白细胞中主要的磷酸二酯酶同工酶，在炎症细胞激活的调节中起关键作用。有四种PDE4亚型（A、B、C和D），并且在每个亚型内有多个变体。最近，我们在单核细胞中发现PDE4B基因表达被脂多糖（LPS）选择性诱导，并且该诱导被白细胞介素（IL）-10和IL-4抑制。在本研究中，我们表明PDE4B基因在中性粒细胞中组成性表达，并且该表达不受LPS或IL-10影响。PDE4B是中性粒细胞以及未刺激或LPS刺激的单核细胞中的主要亚型，并且在这些细胞中，PDE4B2变体是唯一可检测到的PDE4B分子种类。因此，PDE4B2是人类中性粒细胞和单核细胞中主要的磷酸二酯酶同工型，并且其表达在这两种细胞类型中受到不同调节。此外，白细胞是PDE4B2的最主要来源，表明PDE4B2是发现抗炎药物的相对特异性靶点。
