Lipopolysaccharide preconditioning reduces liver metastasis of Colon26 cells by enhancing antitumor activity of natural killer cells and natural killer T cells in murine liver
Lipopolysaccharide preconditioning reduces liver metastasis of Colon26 cells by enhancing antitumor activity of natural killer cells and natural killer T cells in murine liver
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DOI：
10.1111/jgh.15375
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发表时间：
2020-12-31
影响因子：
4.1
通讯作者：
Kishi，Yoji
中科院分区：
文献类型：
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作者：
Nishikawa，Makoto;Kinoshita，Manabu;Kishi，Yoji
背景和目的脂多糖 (LPS) 预处理可显着增强杀菌活性，但减少宿主炎症反应。因此，它可能有益于预防术后感染并发症并减轻手术应激造成的宿主损伤。考虑到其临床应用，LPS预处理如何影响肝脏的抗肿瘤作用是一个重要的问题。然后我们研究了LPS预处理对小鼠Colon26肿瘤细胞抗肿瘤活性的影响。方法连续三天腹腔注射5μg/kg LPS诱导小鼠脂多糖预处理。门静脉内接种表达称为 Nano-lantern 的发光蛋白的 Colon26 细胞，以评估 LPS 预处理对肿瘤肝转移的影响。还在LPS预处理的小鼠中检测了细胞毒性肝淋巴细胞，特别是自然杀伤（NK）细胞和自然杀伤T（NKT）细胞对Colon26细胞的抗肿瘤活性。结果通过IVIS成像系统观察，脂多糖预处理显着阻止了Colon26细胞的肝转移，并延长了肿瘤接种后的存活期。 LPS预处理增加了肝脏NK细胞和NKT细胞的比例和数量，增加了细胞内穿孔素和颗粒酶B的表达，同时降低了细胞内IFN-γ的表达。体外抗肿瘤细胞毒性试验显示，LPS预处理显着增强了肝脏NK细胞和NKT细胞，尤其是NKT细胞对Colon26细胞的抗肿瘤细胞毒性。结论脂多糖预处理有效增强了肝脏NK细胞和NKT细胞的抗肿瘤细胞毒性，从而提高了小鼠门静脉内接种Colon26肿瘤细胞后的存活率。它可能对肿瘤患者的围手术期护理有用。
Background and AimLipopolysaccharide (LPS) preconditioning drastically augments bactericidal activity but reduces the host inflammatory response. Therefore, it may be beneficial to prevent postoperative infectious complications and mitigate host damage by surgical stress. Considering its clinical application, how LPS preconditioning influences the antitumor effect in the liver is an important issue. We then investigated the effect of LPS preconditioning on antitumor activity against Colon26 tumor cells in mice.MethodsLipopolysaccharide preconditioning was induced in mice by the intraperitoneal injection of 5 μg/kg LPS for three consecutive days. Intraportal inoculation of Colon26 cells, which express luminescent protein called Nano‐lantern, was performed to evaluate the effect of LPS preconditioning on tumor liver metastasis. The antitumor activities of cytotoxic liver lymphocytes, especially natural killer (NK) cells and natural killer T (NKT) cells, against Colon26 cells were also examined in LPS preconditioned mice.ResultsLipopolysaccharide preconditioning remarkably prevented liver metastasis of Colon26 cells, as observed by IVIS imaging system, and prolonged survival after tumor inoculation. LPS preconditioning increased the proportions and number of liver NK cells and NKT cells and augmented their intracellular perforin and granzyme B expression, while reducing their intracellular expression of IFN‐γ. Anin vitroantitumor cytotoxicity assay revealed that LPS preconditioning significantly augmented antitumor cytotoxicities of the liver NK cells and NKT cells, especially NKT cells, against Colon26 cells.ConclusionsLipopolysaccharide preconditioning potently augmented antitumor cytotoxicity of liver NK cells and NKT cells, thereby improving mouse survival after intraportal inoculation of Colon26 tumor cells. It may be useful for perioperative care in oncological patients.