Psoriasis is a common chronic inflammatory skin disease that significantly affects patients'quality of life. There is no cure for psoriasis, and available treatments are not completely effective. We have previously found that hydroxytyrosol (HT) has anti-psoriatic effects in vitro. In the present study, we aimed to investigate the therapeutic effects of HT on psoriasis in vivo and to explore the underlying mechanisms. We explored the effects and molecular mechanisms of HT on imiquimod (IMQ)-induced psoriasis-like dermatitis in mice and an M5-induced in vitro cell model using real-time PCR, western blotting, hematoxylin-eosin staining, immunohistochemistry, and enzyme-linked immunosorbent assay. HT (10 mg/kg/d or 50 mg/kg/d, by gavage) ameliorated IMQ-induced clinical manifestations in mice. Moreover, HT ameliorated the histopathological changes and decreased the spleen index and levels of pro-inflammatory cytokines, such as interleukin (IL)-17 A, IL-23, and IL-22, in mouse serum or skin. Mechanistically, HT application inhibited the activation of ERK and NF-кB signaling in the skin samples. Consistently, in vitro analysis showed that HT significantly inhibited inflammation via ERK and NF-κB signaling in a cellular model of psoriasis. Our results indicate that HT alleviates IMQ-induced psoriasis-like dermatitis by inhibiting the ERK and NF-κB signaling pathways, suggesting that HT has a promising therapeutic application in psoriasis treatment.

Psoriasis is a common chronic inflammatory skin disease characterized by aberrant proliferation of keratinocytes and infiltration of immune cells. We previously found that GPR15LG protein is highly expressed in psoriasis lesional skin and it positively regulates psoriatic keratinocyte proliferation. Our data also showed that GPR15LG could regulate the activity of NF-κB pathway which is associated with psoriatic inflammation. In current study, we demonstrated that Gpr15lg (ortholog of GPR15LG) knockdown attenuated the severity of imiquimod (IMQ)-induced psoriasis-like inflammation in mice. Such an effect was achieved by down-regulating the expression of inflammatory cytokines interleukin (IL)-1α, IL-1β, tumor necrosis factor (TNF)-α and S100A7. Consistently, GPR15LG knockdown in vitro significantly downgraded the expression of inflammatory factors in the cellular model of psoriasis. These results suggested that GPR15LG could be involved in the development of psoriasis by regulating inflammation.

Anoikis is a programmed cell death that occurs when cells detach from the extracellular matrix (ECM). Its role in psoriasis remains unclear. This study aims to explore the relationship between psoriasis and apoptosis, focusing on anoikis-related mechanisms. Differentially expressed genes (DEGs) in psoriasis were identified using the GEO database and overlapped with anoikis-related genes from GeneCards to find differentially expressed anoikis-related genes (DE-ARGs). A PPI network was constructed, revealing eight hub DE-ARGs. These were then analyzed using GO, KEGG and ssGSEA. Immune infiltration cells and molecules were examined, and single-cell data analysis, immunohistochemistry, qRT-PCR, Western blotting, gene mapping, and drug prediction were performed. Eighteen DE-ARGs were identified, with STAT3 and BIRC5 as key DEGs. Enrichment analysis showed DE-ARGs were related to the regulation of anoikis and positive regulation of epithelial cell proliferation. Notable differences in dendritic and mast cells were observed between psoriasis lesions and no-lesion samples. Elevated expression of BIRC5 and STAT3 in psoriasis lesions was confirmed through qRT-PCR, western blotting and immunohistochemistry. This study establishes a relationship between anoikis and psoriasis, where STAT3 and BIRC5 play important roles. STAT3 and BIRC5 may serve as potential targets for the prevention and treatment of psoriasis.

Background: Psoriasis is a common chronic inflammatory skin disease characterized by epidermal hyperplasia, inflammatory cell infiltration and excessive neovascularization. It was previously found that C10orf99 regulates keratinocyte proliferation and inflammation in psoriasis. However, the role of C10orf99 on angiogenesis associated with psoriasis is unknown. Methods: We used imiquimod (IMQ)‐induced psoriasis mice and M5‐induced cellular model of psoriasis to research the effects of C10orf99 knockdown on angiogenesis in psoriasis in vivo and in vitro. Results: In this study, our data showed that C10orf99 knockdown ameliorated imiquimod (IMQ)‐induced red plaques in mice and reduced the number of microvessels. Furthermore, we found such an effect was achieved by down‐regulating the expression of vascular endothelial growth factor (VEGF) and metallomatrix proteinase 2 (MMP2). Consistently, C10orf99 knockdown significantly downgraded the expression of MMP2 and VEGF in cellular model of psoriasis. Conclusion: These results suggested that C10orf99 could regulate angiogenesis in psoriasis and it might be a promising potential target of psoriasis.