Psoriasis developed through abnormal crosstalk between the immune cells and epidermal keratinocytes. Apremilast is an oral phosphodiesterase 4 (PDE4) inhibitor and has been approved for the treatment of patients with plaque psoriasis and psoriatic arthritis. Cyclic adenosine monophosphate (cAMP) has a significant role as a secondary messenger and PDE4 degrades intercellular cAMP to AMP. It is widely recognized that PDE4 inhibition by Apremilast increases intracellular cAMP levels in immune cells, thereby in turn suppress the expression of proinflammatory cytokines, such as TNF-α, IFN-γ and IL-23, which are all linked to psoriasis development. However, its direct effect on epidermal keratinocytes have been poorly understood. To this end, we treated normal human epidermal keratinocytes (NHEK) with Apremilast in vitro. Real-time RT-PCR analysis revealed that Apremilast downregulated psoriasis-related gene expression in either unstimulated or cytokine-stimulated NHEK cells. The results suggested that Apremilast directly had an impact not only on immune cells but on keratinocytes presumably through cAMP-mediated damping of psoriasis-related gene expression.

Direct anti-psoriatic effect of Apremilast on epidermal keratinocytes.