Phosphodiesterase 4B2 is the predominant phosphodiesterase species and undergoes differential regulation of gene expression in human monocytes and neutrophils

The type 4 phosphodiesterase (PDE4) is the predominant PDE isozyme in vario us leukocytes and plays a key role in the regulation of inflammatory cell a ctivation. There are four PDE4 subtypes (A, B, C, and D), and within each s ubtype, there are multiple variants. Very recently, we found in monocytes t hat PDE4B gene expression is selectively induced by lipopolysaccharide (LPS ) and that the induction is inhibited by interleukin (IL)-10 and IL-4. In t his study, we show that the PDE4B gene is constitutively expressed in neutr ophils and that this expression remains unaffected by LPS or IL-10. PDE4B i s the predominant subtype in neutrophils and in unstimulated or LPS-stimula ted monocytes, and in these cells, the PDE4B2 variant is the only detectabl e molecular species of PDE4B. Therefore, PDE4B2 is the predominant PDE isof orm in human neutrophils and monocytes, and its expression is regulated dif ferently by these two cell types. Furthermore, leukocytes are the most domi nant source of PDE4B2, suggesting that PDE4B2 is a relatively specific targ et for discovering anti-inflammatory drugs.