Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, No. 218 JiXi Road, Hefei, 230022, Anhui, People's Republic of China.
First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, People's Republic of China.
Eur J Med Res. 2024 Nov 6;29(1):537. doi: 10.1186/s40001-024-02125-7.
Homocysteine (Hcy) is a pro-inflammatory molecule that has the potential to induce oxidative damage to cells and stimulate the release of inflammatory mediators. Hcy has been observed to enhance the production of inflammatory agents in vascular endothelial cells. However, the impact of Hcy on intestinal mucosal inflammation remains largely unexplored. Therefore, the objective of this study was to examine the potential of Hcy to stimulate the synthesis of inflammatory mediators and elucidate the underlying mechanisms in the intestinal mucosa.
A total of 99 patients diagnosed with inflammatory bowel disease (IBD) and 10 healthy individuals were included in this study to assess the impact of homocysteine (Hcy) on the levels of leukotriene E4 (LTE4) and prostaglandin E2 (PGE2). The underlying mechanism responsible for the generation of LTE4 and PGE2 induced by Hcy was investigated using colitis rats and Caco-2 cells. 32 Sprague-Dawley rats were categorized into four groups: normal control, TNBS model, normal with Hcy injection, and TNBS model with Hcy injection. The mRNA expressions of 5-LOX, COX-2, and NF-κB were assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Caco-2 cells were subjected to treatment with varying concentrations (10, 20, 50, 100 μmol/L) of Hcy and incubated for different durations (1, 3, 6 h). The alterations in NF-κB activity, as well as the levels of Hcy, LTE4, and PGE2, were measured using enzyme-linked immunosorbent assay (ELISA).
The excretion of Hcy, LTE4, and PGE2 in urine exhibited significant increases in patients with inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC). In addition, Hcy demonstrated a significant increase in the expression of 5-LOX, COX-2, and NF-κB, as well as elevated levels of LTE4 and PGE2 in rats with colitis. Furthermore, Hcy was found to induce NF-κB activation and nuclear translocation, thereby contributing to the enhanced synthesis of LTE4 and PGE2 in Caco-2 cells.
Hcy was found to enhance the expression of 5-LOX and COX-2 by activating NF-κB, thereby augmenting the production of LTE4 and PGE2, which ultimately exacerbates colonic inflammation in individuals with inflammatory bowel disease (IBD).
同型半胱氨酸（Hcy）是一种促炎分子，有可能诱导细胞氧化损伤并刺激炎症介质的释放。已经观察到 Hcy 增强血管内皮细胞中炎症剂的产生。然而，Hcy 对肠道黏膜炎症的影响在很大程度上仍未得到探索。因此，本研究旨在研究 Hcy 刺激炎症介质合成的潜力，并阐明肠道黏膜中的潜在机制。
本研究纳入了 99 例炎症性肠病（IBD）患者和 10 例健康个体，以评估同型半胱氨酸（Hcy）对白三烯 E4（LTE4）和前列腺素 E2（PGE2）水平的影响。使用结肠炎大鼠和 Caco-2 细胞研究了 Hcy 诱导 LTE4 和 PGE2 产生的潜在机制。将 32 只 Sprague-Dawley 大鼠分为四组：正常对照组、TNBS 模型组、正常 Hcy 注射组和 TNBS 模型 Hcy 注射组。采用逆转录定量聚合酶链反应（RT-qPCR）检测 5-LOX、COX-2 和 NF-κB 的 mRNA 表达。用不同浓度（10、20、50、100 μmol/L）的 Hcy 处理 Caco-2 细胞并孵育不同时间（1、3、6 h），检测 NF-κB 活性的变化以及 Hcy、LTE4 和 PGE2 的水平。
炎症性肠病（IBD）、克罗恩病（CD）和溃疡性结肠炎（UC）患者尿液中 Hcy、LTE4 和 PGE2 的排泄明显增加。此外，结肠炎大鼠中 Hcy 表达 5-LOX、COX-2 和 NF-κB 显著增加，LTE4 和 PGE2 水平升高。此外，Hcy 被发现可诱导 NF-κB 激活和核转位，从而促进 Caco-2 细胞中 LTE4 和 PGE2 的合成。
Hcy 通过激活 NF-κB 增强 5-LOX 和 COX-2 的表达，从而增加 LTE4 和 PGE2 的产生，最终加重 IBD 患者的结肠炎症。
