As a direct consequence of this cytostatic effect, keratinocytes treated with DCE or CS acquired cell motility and were more prone to migrate in functional in vitro scratch-wound assays in response to IL-22. CS and DCE significantly accelerated closure also of untreated scratched cultures, with an efficacy similar to IL-22, indicating that their effect is likely exerted on pathways constitutively activated in keratinocytes. At molecular level, this latter result can be related to the up-regulation of EGFR and ERK1/2, which notoriously are activated by mechanical injury and essential for keratinocyte migration during wound healing process. Also downregulation of p-AKT could be involved in the enhancement of wound closure, as its inhibition is known to accelerate the scratch closure and potentiate the scratch-dependent stimulation of EGF-type growth factor genes. In light of our findings, we can hypothesize the employment of DCE and CS in psoriasis might counteract the pro-inflammatory effects of IFN-c and IL-22 on keratinocytes, as well as to inhibit hyperproliferation in the psoriatic epidermis. Moreover, DCE and CS might revert the apoptosis-resistant phenotype, which is due to intrinsic and acquired alterations of psoriatic keratinocytes. Among alterations, the abnormal activation of the SOCS1-3/ PI3K/AKT and downstream anti-apoptotic NF-kB cascades play a pivotal role in rendering epidermis less susceptible to cytokineinduced apoptosis. While AKT seems to be only slightly Dalasetron Mesylate hydrate downregulated by DCE or CS, NF-kB is strongly inhibited by serquiterpene from Saussurea lappa, and NF-kB inhibition by DCE is known to enhance TNF-a-induced apoptosis of cancer cells. In addition, DCE- and CS-based treatments might be therapeutically relevant also for other skin diseases characterized by uncontrolled proliferation and deficient apoptosis in keratinocytes, including non-melanoma skin cancers. Further studies using terpene lactones in vivo in experimental models of skin hyperproliferative diseases are Epinastine necessary to unveil their therapeutic efficacy, as recently demonstrated for other murine models of inflammatory diseases.