L-Fucose ameliorates DSS-induced acute colitis via inhibiting macrophage M1 polarization and inhibiting NLRP3 inflammasome and NF-kB activation
L-Fucose ameliorates DSS-induced acute colitis via inhibiting macrophage M1 polarization and inhibiting NLRP3 inflammasome and NF-kB activation
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L-岩藻糖通过抑制巨噬细胞 M1 极化和抑制 NLRP3 炎性体和 NF-kB 激活改善 DSS 诱导的急性结肠炎
DOI：
10.1016/j.intimp.2019.05.013
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Hou, Xiaohua
中科院分区：
文献类型：
--
作者：
He, Ruohang;Li, Ying;Hou, Xiaohua
已有研究表明，L-岩藻糖对呼吸系统和皮肤系统有抗炎作用。然而，L-岩藻糖对结肠炎的作用及其潜在机制尚不清楚。本实验研究了L-岩藻糖对右旋糖酐硫酸钠（DSS）诱导的急性结肠炎的抗炎作用和对LPS/ATP诱导的骨髓源性巨噬细胞（BMDM）损伤的体外抗炎作用。我们的研究结果表明，L-岩藻糖显着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-岩藻糖还能抑制巨噬细胞M1极化，抑制NLRP 3炎性小体，减少TNF α、IL 1 β、IL 6等促炎细胞因子的释放。体外研究表明，L-岩藻糖改善了BMDM中由给予LPS和ATP引起的细胞损伤，抑制了NLRP 3炎性小体活化并减少了相应的促炎细胞因子的释放。L-岩藻糖在体内外均能抑制p-NF-kB的表达。总之，我们的研究结果表明，L-岩藻糖可以通过抑制巨噬细胞M1极化，抑制NLRP 3炎性体和NF κ B活化，以及下调促炎细胞因子来减轻结肠炎。
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 TNF alpha, IL1 beta, 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 NFkB activation, and down-regulation of pro-inflammatory cytokines.