Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Int Immunopharmacol. 2019 Aug;73:379-388. doi: 10.1016/j.intimp.2019.05.013. Epub 2019 May 24.
Previous studies reported that L-fucose had anti-inflammatory effects in respiratory and cutaneous system. However, the effect of L-fucose on colitis and the underlying mechanism is poorly understood. We studied the anti-inflammatory effects of L-fucose on Dextran sulfate sodium (DSS)-induced acute colitis in vivo and on LPS/ATP-induced bone marrow derived macrophages (BMDMs) damage in vitro. Our results show that L-fucose significantly alleviated weight loss and disease activity index (DAI) scores in colitis and reduced the infiltration of macrophages and neutrophils. In addition, L-fucose can inhibit macrophage M1 polarization, inactivate the NLRP3 inflammasome and reduce the release of TNFα, IL1β, IL6 pro-inflammatory cytokines. In vitro studies showed that L-fucose ameliorated cell damage resulting from the administration of LPS with ATP in BMDMs, inhibited NLRP3 inflammasome activation and reduced the release of corresponding pro-inflammatory cytokines. Finally, L-fucose can inhibit the expression of p-NF-kB in vivo and in vitro. Overall, our results show that L-fucose can attenuate colitis by inhibiting macrophage M1 polarization, inhibiting NLRP3 inflammasome and NF-kB activation, and down-regulation of pro-inflammatory cytokines.
先前的研究报道，L-岩藻糖在呼吸系统和皮肤系统中具有抗炎作用。然而，L-岩藻糖对结肠炎的作用及其潜在机制尚不清楚。我们研究了 L-岩藻糖对葡聚糖硫酸钠（DSS）诱导的急性结肠炎的体内抗炎作用以及对脂多糖/三磷酸腺苷（LPS/ATP）诱导的骨髓来源巨噬细胞（BMDMs）损伤的体外抗炎作用。我们的结果表明，L-岩藻糖可显著减轻结肠炎的体重减轻和疾病活动指数（DAI）评分，并减少巨噬细胞和中性粒细胞的浸润。此外，L-岩藻糖可抑制巨噬细胞 M1 极化，使 NLRP3 炎性小体失活，并减少 TNFα、IL1β、IL6 等促炎细胞因子的释放。体外研究表明，L-岩藻糖可改善 LPS 与 ATP 联合作用于 BMDMs 引起的细胞损伤，抑制 NLRP3 炎性小体的激活，减少相应促炎细胞因子的释放。最后，L-岩藻糖可抑制体内和体外 p-NF-κB 的表达。综上所述，我们的研究结果表明，L-岩藻糖通过抑制巨噬细胞 M1 极化、抑制 NLRP3 炎性小体和 NF-κB 的激活以及下调促炎细胞因子，可减轻结肠炎。
