Guan Y, Chen J Q, Li X Y, Jiang S N
Department of Ultrasound, The first affiliated Hospital of Hainan Medical University, Hainan, China.
Department of Radiology, Central South University Xiangya School of Medicine affiliated Haikou Hospital, Hainan, China.
J Biol Regul Homeost Agents. 2021 Mar-Apr;35(2):495-504. doi: 10.23812/20-500-A.
Lipopolysaccharide (LPS) plays an important role in tumor suppression by activating macrophages. After macrophages activation, a trail of cytokines was secreted, including IL-1β. Previous studies reported that the anti-tumor function of IL-1β is concentration-dependent, and increasing the level of IL-1β 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-1β. 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-1β. The production of IL-1β was highly enhanced when the macrophages were treated with LPS and ClyA together. The production of IL-1β was regulated by TLR4-MyD88-IL-1β pathway and NLRP3-ASC-Caspase1-IL1β 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-1β 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.
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，会分泌一系列细胞因子，包括IL-1β。先前的研究报道，IL-1β的抗肿瘤功能具有浓度依赖性，提高IL-1β水平会增强其抗肿瘤效果。溶细胞素A（ClyA）是成孔毒素（PFTs）蛋白家族的成员，由革兰氏阴性菌分泌，在增强IL-1β分泌方面具有潜在作用。在本研究中，通过研究溶细胞素A诱导巨噬细胞先天免疫反应的能力以及参与LPS诱导IL-1β产生的信号通路来评估其功能。当巨噬细胞同时用LPS和ClyA处理时，IL-1β的产生显著增强。IL-1β的产生受TLR4-MyD88-IL-1β途径和NLRP3-ASC-Caspase1-IL1β途径调节。用条件培养基处理结肠癌细胞系CT26，CT26细胞的增殖受到抑制，凋亡增加。总之，本研究表明ClyA增强了人巨噬细胞中LPS诱导的IL-1β产生。用巨噬细胞条件培养基处理时，CT26细胞的增殖受到抑制，凋亡增加，这为结肠癌提供了一种可行的治疗方法。
