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

Area of Science:

• Dermatology
• Stem Cell Biology
• Molecular Biology

Background:

• Epidermal stem cells (ESCs) are crucial for skin barrier repair.
• External factors like IL-1α can induce oxidative stress and inflammation, impairing ESC self-repair.
• Apremilast, a phosphodiesterase 4 inhibitor, is approved for psoriasis treatment.

Purpose of the Study:

• To investigate the protective effects of Apremilast on epidermal stem cells (ESCs) against IL-1α-induced dysfunction.
• To elucidate the preliminary mechanism underlying Apremilast's protective action.

Main Methods:

• ESCs were isolated from neonatal mice.
• Key inflammatory markers (TNF-α, IL-8, IL-12), matrix metalloproteinases (MMP-2, MMP-9), and IL-1R1 were quantified via real-time PCR and ELISA.
• Mitochondrial reactive oxygen species (ROS) levels were measured using MitoSOX Red assay.
• Western blot and real-time PCR assessed Myd88, TRAF6, and NF-κB pathway activation (p-NF-κB p65, luciferase activity).
• ESC capacities were evaluated by measuring integrin β1 and Krt19 gene expression.

Main Results:

• IL-1α significantly increased TNF-α, IL-8, IL-12, MMP-2, MMP-9, IL-1R1, and ROS levels, which were markedly reduced by Apremilast.
• Apremilast inhibited the IL-1α-induced activation of the Myd88/TRAF6/NF-κB signaling pathway.
• Apremilast treatment preserved ESC function, evidenced by elevated integrin β1 and Krt19 expression.

Conclusions:

• Apremilast demonstrates protective properties against IL-1α-induced epidermal stem cell (ESC) dysfunction.
• The mechanism involves mitigating oxidative stress and inflammation by inhibiting the Myd88/TRAF6/NF-κB signaling pathway.
• Apremilast may represent a therapeutic strategy for conditions involving ESC damage due to oxidative stress and inflammation.