Interleukin-1β Induces Phosphodiesterase 4B2 Expression in Human Myometrial Cells through a Prostaglandin E2- and Cyclic Adenosine 3′,5′-Monophosphate-Dependent Pathway

Intrauterine infections are important etiological factors of preterm labor. They trigger an increase in proinflammatory cytokines, in particular IL-1β, that induces a cascade of events resulting in the production of potent effectors of myometrial contractility, such as the prostaglandin E2 (PGE2). Within the smooth muscle cells, contractility is under the control of cAMP content, partly regulated by cAMP-phosphodiesterase 4 (PDE4), the predominant family of PDEs expressed in human myometrium. In the present study, using a model of inflammation of human myometrial cells in culture, we demonstrated that exposing the cells to IL-1β resulted in a significant up-regulation of PDE4 activity through an increase in PDE4B2 mRNA and protein levels. The IL-1β-induced PDE4 activity occurs after an increase in PGE2 production and subsequent cAMP augmentation. Pretreatment with indomethacin or NS 398 completely blocked this long-term effect of IL-1β, revealing a PGE2-dependent pathway. Accordingly, our results demonstr...