Anti-Inflammatory Effects of Extracellular Vesicles from on 12-O-Tetradecanoylphorbol-13-Acetate-Induced Skin Inflammation in Mice.

Steroids, which are often used to treat the inflammation associated with various skin diseases, have several negative side effects. As extract has anti-inflammatory effects in various diseases, we evaluated the efficacy of -derived extracellular vesicles (EVEs) in decreasing 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. We determined the effect of the EVEs on the TLR4/NF-κB/NLRP3 inflammasome in human keratinocytes and mouse ear skin. TPA-treated human keratinocytes showed an increased expression of TLR4 and its ligands HMGB1 and S100A8. TPA also increased the expression of (1) NF-κB; (2) the NLRP3 inflammasome components NLRP3, ASC, and caspase 1; and (3) the pyroptosis-related factors GSDMD-NT, IL-18, and IL-1β. However, the expression of these molecules decreased in the TPA-treated human keratinocytes after EVE treatment. Similar to the in vitro results, TPA increased the expression of these molecules in mouse ear skin, and EVE treatment decreased their expression. The TPA treatment of skin increased edema, redness, neutrophil infiltration, and epidermal thickness, and EVE reduced these symptoms of inflammation. In conclusion, the EVEs decreased TPA-induced skin inflammation, which was associated with a decrease in the TLR4/NF-κB/NLRP3 inflammasome.