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-1��-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-��, 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-��B was assessed by measuring the p-NF-��B p65 and luciferase activity. Capacities of ESCs were evaluated by measuring the gene expressions of integrin ��1 and Krt19 using real-time PCR.
RESULTS: Firstly, the expression levels of TNF-��, IL-8, IL-12, MMP-2, MMP-9 and IL-1R1, as well as the ROS level, were significantly elevated by IL-1�� but greatly suppressed by treatment with Apremilast. Subsequently, we found that the activated Myd88/TRAF6/NF-��B signaling pathway induced by stimulation with IL-1�� was significantly inhibited by the introduction of Apremilast. As a result, Apremilast protected ESCs against IL-1��-induced impairment in capacities of ESCs, this was verified by the elevated expression levels of integrin ��1 and Krt19.
CONCLUSIONS: Apremilast might ameliorate IL-1��-induced dysfunction in ESCs by mitigating oxidative stress and inflammation through inhibiting the activation of the Myd88/TRAF6/NF-��B signaling pathway.
