炎症性肠病（IBD）是一种无法治愈的疾病，会对患者的生活质量产生负面影响。目前和新出现的治疗方法针对促炎细胞因子和/或受体来下调促炎反应，但不充分的缓解需要其他治疗方法。在这里，我们报告了合成的抗炎肽15（SAP15）在人巨噬细胞中具有细胞内渗透和抗炎活性。SAP15被荧光标记并用于人白血病单核细胞（THP-1）细胞的细胞内渗透分析。使用生物层干涉法分析了SAP15与组蛋白脱乙酰化酶5（HDAC5）的结合亲和力。对SAP15处理的THP-1细胞进行了蛋白质磷酸化分析、流式细胞术和酶联免疫吸附试验（ELISA）。此外，在一种葡聚糖硫酸钠（DSS）诱导的IBD模型中观察了治疗效应的体内分析。使用ELISA、髓过氧化物酶（MPO）活性测定和组织学评估对SAP15处理的小鼠样本进行了宏观和显微观分析。SAP15已被内化到THP-1细胞的细胞质和细胞核中，并结合到HDAC5蛋白上。对SAP15处理的巨噬细胞进行了蛋白质磷酸化评估，结果显示抑制了HDAC5及其他免疫相关蛋白的磷酸化，导致M2样巨噬细胞标志物的增加，M1样巨噬细胞标志物、肿瘤坏死因子-α和白细胞介素-6细胞因子水平的降低。SAP15治疗对IBD模型显示出结肠长度显著恢复。进一步对结肠进行的组织学分析显示了SAP15的黏膜层的治疗效果。此外，从血浆中的促炎细胞因子水平和MPO活性可以看出，SAP15在减少促炎反应方面起到了有效的作用。这些发现表明SAP15是一种新型具有细胞内渗透特性和抗炎性能的肽，可以作为IBD和其他炎症性疾病的治疗药物。©2023年。韩国组织工程与再生医学学会。

Inflammatory bowel disease (IBD) is an incurable disease that negatively influences the quality of life of patients. Current and emerging therapies target proinflammatory cytokines and/or receptors to downregulate proinflammatory responses, but insufficient remission requires other therapeutic agents. Herein, we report that the synthetic anti-inflammatory peptide 15 (SAP15) is capable of cell penetration and anti-inflammatory activity in human macrophages.SAP15 was labeled with fluorescence and administered to human leukemia monocytic cells (THP-1) cells for cell penetration analysis. Using biolayer interferometry analysis, the binding affinity of SAP15 with histone deacetylase 5 (HDAC5) was measured. SAP15-treated THP-1 cells were analyzed by protein phosphorylation assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). In addition, in vivo analysis of the therapeutic effect on IBD was observed in a dextran sulfate sodium (DSS)-induced model. Samples from SAP15-treated mice were analyzed at both the macroscopic and microscopic levels using ELISA, myeloperoxidase (MPO) assays, and histological evaluations.SAP15 was internalized within the cytosol and nucleus of THP-1 cells and bound to the HDAC5 protein. SAP15-treated macrophages were assessed for protein phosphorylation and showed inhibited phosphorylation of HDAC5 and other immune-related proteins, which led to increased M2-like macrophage markers and decreased M1-like macrophage markers and tumor necrosis factor-α and interleukin-6 cytokine levels. The SAP15 treatment on IBD model showed significant recovery of colon length. Further histological analysis of colon demonstrated the therapeutic effect of SAP15 on mucosal layer. Moreover, proinflammatory cytokine levels and MPO activity from the plasma show that SAP15 is effective in reduced proinflammatory responses.These findings suggest that SAP15 is a novel peptide with a novel cell-penetrating peptide with anti-inflammatory property that can be used as a therapeutic agent for IBD and other inflammatory diseases.© 2023. Korean Tissue Engineering and Regenerative Medicine Society.