論文の公開元へCutaneous Liver X Receptor Activation Prevents the Formation of Imiquimod-Induced Psoriatic Dermatitis
概要
Psoriasis is a chronic inflammatory and proliferative skin disorder. Crosstalk of inflammatory cytokines and lipid mediators in the epithelial–immune microenvironment of the skin is involved in psoriasis development, which is stimulated by the disorder of lipid metabolism. Liver X receptors (LXRs) are known to regulate lipid metabolism and inflammation, but their role in psoriasis has not been fully investigated.
In order to investigate the role of LXR in psoriasis, I topically applied LXR agonist, GW3965 on imiquimod-induced psoriasis mice model for 7 days. I found that topical LXR activation prevented the development of imiquimod-induced psoriatic dermatitis in mice. To further understand the effect on activated LXR in preventing imiquimod-induced psoriasis on a transcriptomic and lipid mediator level, I performed real-time quantitative polymerase chain reaction to evaluate the level of psoriasis-related genes and lipidomic respectively. Transcriptional and lipidomic analyses revealed that topical GW3965 downregulated the expression of psoriasis-related genes, such as Cxcl1, Cxcl2, Ccl20, Il1a, Il1b, Il17a, and Il23, and reduced the expression levels of cyclooxygenase-2 and production of prostanoids in the lesional skin. In vitro analysis demonstrated that GW3965 reduced the expression of psoriasis-related genes in keratinocytes stimulated by interleukin-1β or imiquimod.
In conclusion, cutaneous LXR activation prevents the development of psoriasis in an animal model. The results highlight the suppression in the production of arachidonic acid metabolism in the development of psoriasis and propose LXR and its response genes as the potential therapeutic targets.
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