ClyA enhances LPS-induced IL-1β secretion in human macrophages through TLR4 and NLRP3 signaling
ClyA enhances LPS-induced IL-1β secretion in human macrophages through TLR4 and NLRP3 signaling
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ClyA 通过 TLR4 和 NLRP3 信号传导增强人类巨噬细胞中 LPS 诱导的 IL-1β 分泌。
DOI：
10.23812/20-500-a
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发表时间：
2021-03-01
影响因子：
3.2
通讯作者：
Jiang, S. N.
中科院分区：
文献类型：
--
作者：
Guan, Y.;Chen, J. Q.;Jiang, S. N.
脂多糖（LPS）通过激活巨噬细胞在肿瘤抑制中发挥重要作用。巨噬细胞激活后，分泌一系列细胞因子，包括IL-1 β。既往研究报道IL-1 β的抗肿瘤功能具有浓度依赖性，升高IL-1 β的水平会增强其抗肿瘤作用。胞溶素A （ClyA）是蛋白质家族的一员，被称为成孔毒素（pft），由革兰氏阴性菌分泌，它在增强IL-1 β的分泌中具有潜在的作用。在本研究中，通过研究其在巨噬细胞中诱导先天免疫反应的能力以及参与lps诱导IL-1 β产生的信号通路来评估细胞溶素A的功能。LPS和ClyA同时作用于巨噬细胞时，IL-1 β的产生明显增强。IL-1 β的产生受TLR4-MyD88-IL-1 β途径和nlrp3 - asc - caspase1 -IL-1 β途径的调控。用条件培养基处理结肠癌细胞系CT26，抑制CT26细胞的增殖，增加CT26细胞的凋亡。综上所述，本研究表明，ClyA可增强LPS诱导的人巨噬细胞IL-1 β的产生。巨噬细胞条件培养基抑制CT26细胞增殖，增加细胞凋亡，为结肠癌提供了一种可行的治疗方法。
Lipopolysaccharide (LPS) plays an important role in tumor suppression by activating macrophages. After macrophages activation, a trail of cytokines was secreted, including IL-1 beta. Previous studies reported that the anti-tumor function of IL-1 beta is concentration-dependent, and increasing the level of IL-1 beta will enhance its anti-tumor effect. Cytolysin A (ClyA), a member of the protein family called pore-forming toxins (PFTs), is secreted by Gram-negative bacteria, which has a potential role in enhancing the secretion of IL-1 beta. In this study, the function of Cytolysin A was evaluated by investigating its ability to induce innate immune responses in macrophages and the signaling pathway(s) involved in LPS-induced production of IL-1 beta. The production of IL-1 beta was highly enhanced when the macrophages were treated with LPS and ClyA together. The production of IL-1 beta was regulated by TLR4-MyD88-IL-1 beta pathway and NLRP3-ASC-Caspase1-IL1 beta pathway. By treating the colon cancer cell line CT26 with the conditioned medium, the proliferation of CT26 cells was inhibited and the apoptosis of CT26 cells was increased. In conclusion, this study indicated that ClyA enhances the production of IL-1 beta induced by LPS in human macrophages. The proliferation of CT26 cells was inhibited and the apoptosis was increased when being treated with the macrophage-conditioned media, which provides a feasible treatment for colon tumor.