Pi-Wei Institute, Guangzhou University of Chinese Medicine, China.
State Key Laboratory of Applied Microbiology in Southern China, Guangdong Institute of Microbiology, China.
Biomed Pharmacother. 2018 Sep;105:781-788. doi: 10.1016/j.biopha.2018.06.011. Epub 2018 Jun 15.
Regulatory T (Treg) cells and T helper 17 (Th17) cells play crucial roles in ulcerative colitis (UC). Kuijieling (KJL) is an effective Chinese medicine formula for treating UC in clinic. Kuijieling has shown remedy effect on the imbalance between Treg and Th17 cells. This study aimed to further reveal the exact underlying mechanism of how Kuijieling regulates the differentiation of Treg and Th17 cells in the treatment of UC.
Colitis was induced by trinitrobenzene sulfonic acid in rats and treated by KJL. Pathological injury was evaluated by HE staining and pathological score. Transforming growth factor-β1 (TGF-β1), interleukin(IL)-2, IL-6, IL-10, IL-17, IL-23 and IL-21 in plasma were assayed by ELISA. Forkhead box P3 (Foxp3), signal transducer and activator of transcription (STAT) 5 expressed in colon mucosa were measured by western blot. Immunohistochemistry was employed for quantifying retinoic acid-related orphan receptor γt (RORγt) and STAT3 in colon. RT-PCR was used to analyze the expression of IL-2, IL-17, IL-23, IL-21 mRNA in colon.
After the administration of KJL, pathological injury in colon mucosa was reduced and histological score was decreased, transforming growth factor-β1 (TGF-β1), interleukin(IL)-2, IL-10 in blood and Foxp3, STAT5, IL-2 in colon increased significantly, IL-6, IL-23, IL-17, IL-21 in blood and RORγt, STAT3, IL-23, IL-17, IL-21 in colon decreased. Our result showed that KJL regulates the related cytokines and transcription factors to promote Treg cells and suppress Th17 cells.
KJL restores the balance between Treg and Th17 cells through regulating the differentiation of them, therefore contributes to the treatment of UC.
调节性 T（Treg）细胞和辅助性 T 细胞 17（Th17）在溃疡性结肠炎（UC）中发挥重要作用。溃结灵（KJL）是一种有效的治疗 UC 的中药方剂。溃结灵对 Treg 和 Th17 细胞失衡具有治疗作用。本研究旨在进一步揭示溃结灵调节 Treg 和 Th17 细胞分化治疗 UC 的确切作用机制。
采用三硝基苯磺酸诱导大鼠结肠炎，并用 KJL 进行治疗。通过 HE 染色和病理评分评估病理损伤。通过 ELISA 测定血浆中转化生长因子-β1（TGF-β1）、白细胞介素（IL）-2、IL-6、IL-10、IL-17、IL-23 和 IL-21。采用 Western blot 检测结肠黏膜中叉头框 P3（Foxp3）和信号转导及转录激活因子 5（STAT）5 的表达。采用免疫组化法测定结肠中维甲酸相关孤儿受体γt（RORγt）和 STAT3 的含量。采用 RT-PCR 分析结肠中 IL-2、IL-17、IL-23、IL-21 mRNA 的表达。
KJL 给药后，结肠黏膜病理损伤减轻，组织学评分降低，血液中 TGF-β1、IL-2、IL-10 和结肠中 Foxp3、STAT5、IL-2 明显增加，血液中 IL-6、IL-23、IL-17、IL-21 和结肠中 RORγt、STAT3、IL-23、IL-17、IL-21 明显降低。结果表明，KJL 通过调节相关细胞因子和转录因子来促进 Treg 细胞的分化，抑制 Th17 细胞的分化。
KJL 通过调节 Treg 和 Th17 细胞的分化来恢复 Treg 和 Th17 细胞之间的平衡，从而有助于 UC 的治疗。
