| Abstract: | Endocannabinoids (ECs) are important regulators of cell signalling. Cannabinoid receptors are involved in keratinocyte proliferation/differentiation. Elevation of the endogenous cannabinoid tone leads to strong anti‐inflammatory effects. Here, we explored the influence of endocannabinoid system (ECS) modulators on skin permeability barrier repair, epidermal proliferation, differentiation and inflammation in hairless mice. We used WOBE440, a selective fatty acid amide hydrolase (FAAH) inhibitor, WOL067‐531, an inhibitor of endocannabinoid reuptake with no relevant FAAH activity, which both signal via cannabinoid receptor‐1 and cannabinoid receptor‐2 (CB‐1R and CB‐2R) and compared them to WOBE15 which signals via CB‐2R. Barrier disruption and skin irritation were induced by tape stripping or by sodium dodecyl sulphate (SDS) patch testing. Immediately after barrier disruption, 30 μL of 0.5% WOBE440, WOL067‐531 and WOBE15 solutions or the vehicle was applied topically. Barrier repair was monitored by transepidermal water loss at 1.5, 3, 5 and 7 hours. We found that barrier repair was significantly delayed by WOL067‐531. A tendency for a delay was noticed for WOBE440, whereas for WOBE15, no effect was observed. Immunohistology showed that the tape‐stripping‐induced increase in epidermal proliferation and filaggrin expression was significantly reduced by topical applications of WOL067‐531 and WOBE440, but not by WOBE15. Also, the SDS‐induced inflammation, as determined by the number of inflammatory cells, was reduced by WOL067‐531 and WOBE440. In summary, we showed that WOL067‐531 exhibits a significant effect on skin barrier repair, epidermal proliferation/differentiation and inflammation. |
