Fig. 1.

Schematic illustration of how PDE4 inhibitors and cAMP are involved in resolving inflammation. Increased level of cAMP inhibits the production of pro-inflammatory cytokines through simultaneous inhibition of PKA-NFkB and Epac1/2-NFkB pathways; and promotes the production of anti-inflammatory mediators by activation of the PKA-CREB pathway. The intracellular level of cAMP is mainly controlled by the activity of adenylyl cyclase (AC) and phosphodiesterase 4 (PDE4). Upon stimulation, AC increases cAMP levels by converting ATP to cAMP. PDE4 controls the amplitude and duration of the cAMP signal by catalyzing the degradation of cAMP to AMP. Inhibition of PDE4 increases the intracellular levels of cAMP. Adenylyl cyclase (AC), phosphodiesterase 4 (PDE4), protein kinase A (PKA), exchange protein 1/2 activated by cAMP (Epac1/2), phosphorylated cAMP-responsive element binding protein (pCREB), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), inhibitor of PDE4 (PDE4i)

The figure was created with assistance from Erik Nylund, VisualizeThat AB