Department of Medical Technology, School of Life and Environmental Science, Azabu University, Sagamihara 252-5201, Japan.
Research Institute for Healthy Living, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-0841, Japan.
Int J Mol Sci. 2023 Sep 21;24(18):14387. doi: 10.3390/ijms241814387.
Lipopolysaccharide (LPS) is a bacterial component that activates intracellular signaling pathways upon binding to the Toll-like receptor (TLR)-4/MD-2 complex. It is well known that LPS injected into animals and high-dose (100 ng/mL to 1 μg/mL) LPS treatment to innate immune cells induce an inflammatory response. In contrast, LPS is naturally present in the gastrointestinal tract, respiratory tract, and skin of humans and animals, and it has been shown that TLR-4-deficient animals cannot maintain their immune balance and gut homeostasis. LPS from commensal bacteria can help maintain homeostasis against mucosal stimulation in healthy individuals. Oral LPS administration has been shown to be effective in preventing allergic and lifestyle-related diseases. However, this effect was not observed after treatment with LPS at high doses. In mice, oral LPS administration resulted in the detection of LPS at a low concentration in the peritoneal fluid. Therefore, LPS administered at low and high doses have different effects. Moreover, the results of in vitro experiments using low-dose LPS may reflect the effects of oral LPS administration. This review summarizes the utility of in vitro models using cells stimulated with LPS at low concentrations (50 pg/mL to 50 ng/mL) in elucidating the mechanisms of oral LPS administration. Low-dose LPS administration has been demonstrated to suppress the upregulation of proinflammatory cytokines and promote wound healing, suggesting that LPS is a potential agent that can be used for the treatment and prevention of lifestyle-related diseases.
脂多糖（LPS）是一种细菌成分，与 Toll 样受体（TLR）-4/MD-2 复合物结合后会激活细胞内信号通路。众所周知，将 LPS 注射到动物体内和用高剂量（100ng/mL 至 1μg/mL）LPS 处理先天免疫细胞会引发炎症反应。相比之下，LPS 天然存在于人和动物的胃肠道、呼吸道和皮肤中，已经表明 TLR-4 缺陷型动物无法维持其免疫平衡和肠道内稳态。来自共生细菌的 LPS 有助于维持健康个体对黏膜刺激的内稳态。口服 LPS 给药已被证明可有效预防过敏和生活方式相关疾病。然而，在用高剂量 LPS 治疗后未观察到这种效果。在小鼠中，口服 LPS 给药导致在腹腔液中检测到低浓度的 LPS。因此，低剂量和高剂量的 LPS 具有不同的作用。此外，使用低浓度 LPS 进行的体外实验结果可能反映了口服 LPS 给药的效果。这篇综述总结了使用低浓度 LPS（50pg/mL 至 50ng/mL）刺激细胞的体外模型在阐明口服 LPS 给药机制方面的效用。低剂量 LPS 给药已被证明可抑制促炎细胞因子的上调并促进伤口愈合，表明 LPS 是一种有潜力的可用于治疗和预防生活方式相关疾病的药物。
