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Background: Psoriasis is an autoimmune disease that iscaused by a shift in the Th1/Th2 balance toward Th1-dominant immunity. It has been established as an effectivetreatment to counteract psoriasis by subcutaneous injectionof recombinant interleukin (IL)-4, and IL-4 gene therapy bytopical transdermal penetration has shown its antipsoriaticeffect in mice. Retinoic acid (RA) and dimethylsulfoxide canincrease the efficiency of gene transfection in the topicaltransdermal delivery system. Objective: We investigatedwhether RA could improve anti-psoriasis efficiency usingIL-4 expression plasmid pORF-mIL-4 (pIL-4) via transdermaldelivery system in K14-vascular endothelial growth (K14-VEGF) factor transgenic mice. Methods: After pretreatmentwith RA, plasmid pIL-4 in 10% dimethylsulfoxide wasapplied to the ear skin by topical transdermal penetration. Hematoxylin- eosin staining and immunohistochemistrywere performed with ear samples to evaluate anti-psoriasisefficiency in mice. Results: The psoriasis pathologicalfeatures were relieved and psoriasis-associated factors weresignificantly reduced. Conclusion: Our results reveal thattopical application of pIL-4 in dimethylsulfoxide by transdermaldelivery with RA pretreatment can improve psoriasissignificantly.