乾癬是慢性發炎的皮膚疾病，在乾癬的病變部位會有角質細胞不正常的增生和分化、血管新生和免疫細胞的浸潤。浸潤的免疫細胞會表現Th1和Th17相關的細胞激素和生長因子。雖然細胞激素的pre-mRNA在真核細胞的半衰期很短，這和pre-mRNA的3’端非轉譯區包括富含AU序列有關。這段序列會被human antigen R (HuR) 辨識，以增加pre-mRNA的穩定性和促使pre-mRNA從細胞核運輸到細胞質進行轉譯。先前的研究指出HuR分佈在細胞核和細胞質，並在乾癬的病變部位會增加mRNA的穩定性。HuR能結合到多個和乾癬病變有關的mRNA，因此HuR可能對乾癬治療是有潛力的標靶。我們發現寡胜肽JS-1對HuR有結合能力。利用imiquimod C57BL/6和BALB/c小鼠誘發類似乾癬症狀的皮膚炎，並用JS-1進行治療，發現JS-1能夠改善乾癬的症狀。我們也探討JS-1在各組織的分佈情況和對特定組織的影響，以及發現JS-1注射到體內後會分佈在皮膚病變部位、脾臟和肝臟。測定小鼠的肝功能發現JS-1會降低alanine transaminase (ALT)和aspartate transaminase (AST)指數，顯示JS-1可降低乾癬相關的肝發炎，並未對肝臟造成損害。從細胞實驗，我們發現JS-1能減少受imiquimod 刺激的Raw 264.7細胞產生IL-23和TNFα的量，並造成細胞的凋亡。總結，我們的研究提供對乾癬新穎的治療策略。

Psoriasis is a common chronic inflammatory skin disease, characterized by abnormal differentiation and proliferation of keratinocytes, angiogenesis, and infiltration of inflammatory cells that secrete Th1- and Th17-associated cytokines in the skin lesion, such as TNF-α, IL-17, and IL-20. Although mRNAs that encode cytokines are short-lived mRNAs in eukaryotes, the pre-mRNAs, which contain AU-rich elements (AREs) and recognized and stabilized by human antigen R (HuR), an RNA-binding protein, for post-transcription. Previous studies have suggested that HuR is involved in the stabilization of mRNAs in the psoriatic skin. HuR distributes in the cytoplasm and nucleus of psoriatic keratinocytes. Furthermore, HuR can bind numerous transcripts involved in the pathogenesis of psoriasis. Therefore, HuR may be a potential therapeutic target for psoriasis. We tested a novel oligopeptide, designated JS-1, for binding to the RNA-binding site of HuR as a therapeutic agent for psoriasis. We used imiquimod to induce psoriasis-like dermatitis in C57BL/6 and BALB/c mice. The psoriasis symptoms were improved in mice with imiquimod-induced dermatitis after treatment with the oligopeptide JS-1. Examination of the JS-1 distribution in mice revealed that JS-1 was mainly accumulated in the psoriatic skin, spleen, and liver. Furthermore, treatment with JS-1 decreased serum AST and ALT levels in mice, indicating that JS-1 can reduce psoriasis-related liver inflammation and induce no hepatotoxiciy. Furthermore, JS-1 treatment reduced TNF-α and IL-23 production and induced apoptosis in Raw 264.7 cells upon stimulation with imiquimod. Collectively, this study may provide a novel therapeutic strategy for psoriasis.

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