Phosphodiesterases 4 (PDE4) act as proinflammatory enzymes via degradation of 
cAMP, whereas PDE4 inhibitors play an anti-inflammatory role in vitro and in 
vivo. In particular, apremilast has been recently approved for the treatment of 
psoriasis and psoriatic arthritis. However, little is known on the expression 
pattern of PDE4 in psoriasis. We report that PDE4B and PDE4D mRNA are 
overexpressed in peripheral blood mononuclear cells (PBMC) from psoriasis, as 
compared with normal controls, while apremilast reduces PBMC production of a 
number of pro-inflammatory cytokines and increases the levels of 
anti-inflammatory mediators. PDE4 expression is up-regulated in psoriatic dermis 
as compared with normal skin, with particular regard to fibroblasts. This is 
confirmed in vitro, where both dermal fibroblasts (DF) and, to a greater extent, 
myofibroblasts (DM) express all PDE4 isoforms at the mRNA and protein level. 
Because PDE4 interacts with the nerve growth factor (NGF) receptor CD271 in lung 
fibroblasts, we evaluated the relationship and function of PDE4 and CD271 in 
normal human skin fibroblasts. All PDE4 isoforms co-immunoprecipitate with CD271 
in DM, while apremilast inhibits apoptosis induced by β-amyloid, a CD271 ligand, 
in DM. Furthermore, apremilast significantly reduces NGF- and transforming 
growth factor-β1 (TGF-β1)-induced fibroblast migration, and inhibits DF 
differentiation into DM mediated by NGF or TGF-β1. Finally, in DM, apremilast 
significantly reduces cAMP degradation induced by treatment with β-amyloid. 
Taken together, these results indicate that PDE4 play an important role in 
psoriasis. In addition, the study reveals that the PDE4/CD271 complex could be 
important in modulating fibroblast functions.