Liu Ruixian, Zhang Zhe, Zhou Chuan, Wang Binbin, Zhang Muhan, Sun Yaxing, Yao Yao, Zhang Yanru, He Yijia, Yu Junzhi, Xia Yimeng, Liu Yan, Ning Shiyang, Feng Baisui
Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Immunol. 2025 May 9;16:1558845. doi: 10.3389/fimmu.2025.1558845. eCollection 2025.
Inflammatory bowel disease (IBD) is a complex immune-mediated condition, and biologics are the most commonly used drugs for its treatment. However, there are still cases of ineffective treatment. B-cell lymphoma 6 (Bcl6), a transcriptional suppressor, is known to have regulatory effects on multiple immune-associated cell subsets. FX1, a novel specific BCL6 Bric-à-brac (BTB) inhibitor, has shown positive effects in many disease models, but its effects and mechanisms in IBD control remain unclear.
We observed colon length and DAI score of colitis mice after treatment. HE staining section was used to evaluate colonic injury, while the expression of colonic pro-inflammatory cytokines by RT-qPCR. And differences in immune cell subsets between the two groups was analyzed by flow cytometry. Additionally, IHC and RT-qPCR were employed to evaluate the expression of colonic tight junction proteins. Furthermore, RAW264.7 cells and co-cultured Caco2 cells were detected by ELISA and RT-qPCR.
In the treat group, colitis symptoms in mice were significantly improved, and there was a decrease in proportion of macrophages and protection of intestinal mucosal integrity-indicating anti-inflammatory effects of FX1. In cell experiments, we found that FX1 decreased secretion of pro-inflammatory factors by macrophages and increased expression of tight junction proteins in Caco2 cells after co-culture.
The experimental findings demonstrate the inhibitory effect of FX1 on inflammation in murine colitis model as well as its potential mechanism. BCL6 is a potential target for treating IBD.
炎症性肠病（IBD）是一种复杂的免疫介导性疾病，生物制剂是治疗该病最常用的药物。然而，仍有治疗无效的病例。转录抑制因子B细胞淋巴瘤6（Bcl6）对多种免疫相关细胞亚群具有调节作用。FX1是一种新型的特异性BCL6 Bric-à-brac（BTB）抑制剂，在许多疾病模型中已显示出积极作用，但其在IBD控制中的作用和机制仍不清楚。
我们观察了治疗后结肠炎小鼠的结肠长度和疾病活动指数（DAI）评分。用苏木精-伊红（HE）染色切片评估结肠损伤，同时用逆转录定量聚合酶链反应（RT-qPCR）检测结肠促炎细胞因子的表达。通过流式细胞术分析两组免疫细胞亚群的差异。此外，采用免疫组织化学（IHC）和RT-qPCR评估结肠紧密连接蛋白的表达。进一步地，通过酶联免疫吸附测定（ELISA）和RT-qPCR检测RAW264.7细胞和共培养的Caco2细胞。
在治疗组中，小鼠的结肠炎症状明显改善，巨噬细胞比例降低，肠黏膜完整性得到保护，表明FX1具有抗炎作用。在细胞实验中，我们发现FX1可减少巨噬细胞分泌促炎因子，并增加共培养后Caco2细胞中紧密连接蛋白的表达。
实验结果证明了FX1对小鼠结肠炎模型炎症的抑制作用及其潜在机制。BCL6是治疗IBD的一个潜在靶点。
