Lipopolysaccharide-induced DC-SIGN/TLR4 crosstalk activates NLRP3 inflammasomes via MyD88-independent signaling in gastric epithelial cells
Lipopolysaccharide-induced DC-SIGN/TLR4 crosstalk activates NLRP3 inflammasomes via MyD88-independent signaling in gastric epithelial cells
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DOI：
10.1016/j.yexcr.2020.112292
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发表时间：
2020-11-01
影响因子：
3.7
通讯作者：
Xu, Chundi
中科院分区：
文献类型：
--
作者：
Chen, Yufan;Huang, Jiebin;Xu, Chundi
异常模式识别受体（PRR）信号在胃微生物群引起的胃粘膜损伤中起重要作用;然而，潜在的分子机制仍不清楚。在这里，我们表明，DC-SIGN，树突状细胞的表面表型标志物，在胃上皮细胞面临LPS刺激过表达。NLRP 3在胃上皮细胞中的表达显著增加，并与LPS刺激的程度有关。此外，DC-SIGN可与TLR 4相互作用，通过MyD 88非依赖性信号通路促进NLRP 3及相关基因表达，调节胃上皮细胞IL-1 β和IL-18的分泌。流式细胞仪分析结果表明，DC-SIGN主要介导的Th 1分化时，与胃上皮细胞共培养。这些结果表明，LPS诱导的DC-SIGN表达通过MyD 88非依赖性TLR 4信号通路调节胃上皮细胞NLRP 3炎性小体的形成，并诱导Th 1优势的宿主免疫应答，这些发现可能表明DC-SIGN在非免疫细胞中的新功能，并阐明胃上皮细胞在微生物植物群引起的免疫损伤机制中的多样性作用。
Abnormal pattern recognition receptor (PRR) signaling plays an important role in gastric mucosal damage caused by stomach microbiota; however, the underlying molecular mechanisms remain obscure. Here, we show that DC-SIGN, a surface phenotype marker of dendritic cells, is overexpressed in gastric epithelial cells facing LPS stimulation. NLRP3 expression in gastric epithelial cells are significantly increased and related to the degree of LPS stimulation. Furthermore, DC-SIGN could interact with TLR4, promote NLRP3 and related genes expression via MyD88-independent signaling pathway and regulate the secretion of IL-1 beta and IL-18 in gastric epithelial cells. The results of flow cytometry analysis show that DC-SIGN primarily mediates Th1 differentiation when co-cultured with gastric epithelial cells. These results reveal that LPS-induced DC-SIGN expression modulates NLRP3 inflammasomes formation via MyD88-independent TLR4 signaling in gastric epithelial cell, and induces a Th1-predominant host immune response,these findings may indicate a new function of DC-SIGN in non-immune cells, and elucidate the diversity role of gastric epithelial cells in mechanism of immune damage caused by microbial flora.