BACKGROUND Uveitis is a potentially sight-threatening form of ocular inflammation that affects the uvea in the wall of the eye. Currently available treatments for uveitis have exhibited profound adverse side effects. However, KS23 is a novel 23-amino-acid anti-inflammatory peptide derived from adiponectin that may have the capability to function as a safe alternative to these existing treatment options. We, therefore, evaluated the preventive effect of KS23 in experimental autoimmune uveitis (EAU). METHODS EAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 161-180 (IRBP161-180). KS23 was then administered every 2 days via intraperitoneal injection to induce protection against EAU. Clinical and histopathological scores were employed to evaluate the disease progression. Inflammatory cytokines were also quantified using ELISA, and the expression levels of specific chemokines and chemokine receptors were assessed via qRT-PCR. In addition, the proportions of Th1 and Th17 cells were detected via flow cytometry, and the expression levels of specific proteins were quantified from the retina of mice using western blot analysis, to elucidate the specific mechanism of action employed by KS23 to suppress the inflammation associated with EAU. RESULTS KS23 was found to significantly improve EAU-associated histopathological scores, while decreasing the expression of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6, and IL-17A), chemokines (LARC, RANTES, MIG, IP-10), and chemokine receptors (CCR6 and CXCR3). The proportions of Th1 and Th17 cells were also suppressed following intraperitoneal injection with KS23. The anti-inflammatory mechanism employed by KS23 was determined to be associated with the activation of AMPK and subsequent inhibition of NF-κB. CONCLUSIONS KS23 decreased the proportions of Th1 and Th17 cells to effectively ameliorate the progression of EAU. It may, therefore, serve as a promising potential therapeutic agent for uveitis.

中文翻译：

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KS23是一种衍生自脂联素的新型肽，可抑制视网膜炎症并在实验性自身免疫性葡萄膜炎期间下调Th1和Th17细胞的比例。

背景技术葡萄膜炎是一种潜在的威胁视觉的眼部炎症形式，其会影响眼壁中的葡萄膜。目前可用于葡萄膜炎的治疗表现出深远的不良副作用。但是，KS23是一种新的23氨基酸抗炎肽，衍生自脂联素，可以作为这些现有治疗方法的安全替代品。因此，我们评估了KS23在实验性自身免疫性葡萄膜炎（EAU）中的预防作用。方法通过用肽间感光素类视黄醇结合蛋白161-180（IRBP161-180）免疫，在小鼠中诱导EAU。然后每两天通过腹膜内注射施用KS23以诱导针对EAU的保护。使用临床和组织病理学评分来评估疾病进展。炎症细胞因子也使用ELISA进行定量，并通过qRT-PCR评估特定趋化因子和趋化因子受体的表达水平。此外，通过流式细胞术检测Th1和Th17细胞的比例，并使用Western blot分析从小鼠视网膜中定量特定蛋白的表达水平，以阐明KS23抑制炎症相关分子的特定作用机制。与EAU。结果发现KS23可显着改善EAU相关的组织病理学评分，同时降低促炎细胞因子（IFN-γ，TNF-α，IL-6和IL-17A），趋化因子（LARC，RANTES，MIG，IP）的表达-10）和趋化因子受体（CCR6和CXCR3）。在腹腔内注射KS23后，Th1和Th17细胞的比例也被抑制。KS23所采用的抗炎机制被确定与AMPK的激活和随后对NF-κB的抑制有关。结论KS23降低了Th1和Th17细胞的比例，以有效改善EAU的进程。因此，它可以作为葡萄膜炎的有希望的潜在治疗剂。