Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells

Background and purpose: Skin tissue is the natural barrier that protects our body, the damage of which can be repaired by the epidermal stem cells (ESCs). However, external factors abolish the self-repair ability of ESCs by inducing oxidative stress and severe inflammation. Apremilast is a small molecular inhibitor of phosphodiesterase 4 that was approved for the treatment of psoriasis. In the present study, the protective property of Apremilast against IL-1α-induced dysfunction on epidermal stem cells, as well as the preliminary mechanism, will be investigated. Methods: ESCs were isolated from neonatal mice. The expression levels of TNF-α, IL-8, IL-12, MMP-2, and MMP-9 were detected using real-time PCR and ELISA. MitoSOX Red assay was used to determine the level of mitochondrial reactive oxygen species (ROS). Western blot and real-time PCR were utilized to determine the expression levels of IL-1R1, Myd88, and TRAF6. Activation of NF-κB was assessed by measuring the p-NF-κB p65 and luciferase activity. Capacities of ESCs were evaluated by measuring the gene expressions of integrin β1 and Krt19 using real-time PCR. Results: Firstly, the expression levels of TNF-α, IL-8, IL-12, MMP-2, MMP-9 and IL-1R1, as well as the ROS level, were significantly elevated by IL-1α but greatly suppressed by treatment with Apremilast. Subsequently, we found that the activated Myd88/TRAF6/NF-κB signaling pathway induced by stimulation with IL-1α was significantly inhibited by the introduction of Apremilast. As a result, Apremilast protected ESCs against IL-1α-induced impairment in capacities of ESCs, this was verified by the elevated expression levels of integrin β1 and Krt19. Conclusions: Apremilast might ameliorate IL-1α-induced dysfunction in ESCs by mitigating oxidative stress and inflammation through inhibiting the activation of the Myd88/TRAF6/NF-κB signaling pathway.