Ghadimi Darab, Fölster-Holst Regina, Blömer Sophia, Ebsen Michael, Röcken Christoph, Uchiyama Jumpei, Matsuzaki Shigenobu, Bockelmann Wilhelm
Department of Microbiology and Biotechnology, Max Rubner-Institut, Hermann-Weigmann-Str 1, D-24103, Kiel, Germany.
Department of Allergology and Dermatology, University Hospital Schleswig-Holstein, Schittenhelmstr. 7, D-24105, Kiel, Germany.
Biochimie. 2025 Apr;231:35-45. doi: 10.1016/j.biochi.2024.12.001. Epub 2024 Dec 6.
Plant sterols (PSs) exhibit intrinsic functions such as antibacterial effects. Their effects simultaneously on both host-mediated and bacteria-mediated pathogenesis are not yet fully understood. We hypothesized that when absorptive cells, defensive cells and detoxer cells are cultured together, their convergent response to an infectious pathogen depends on the molecular mimicry between the ingested sterols and their own defensive lipids. A human triple cell co-culture model incorporating colonocytes, macrophages, and hepatocytes was established. Cocultures were stimulated with Klebsiella pneumoniae 52145 (Kp52145) in the presence of pure plant sterol (β-sitosterol, PS) for 6 h. Changes in the structural health markers of the stimulated cocultured cells and their immune response and biochemical markers of pathogenicity were determined. PS significantly inhibited the secretion of cytokines induced by Kp52145. Cell viability was higher in the Kp52145 + PS group compared to the Kp52145 alone group. PS decreased Kp52145-induced marker of pathogenicity (SOD), accompanied by reduced levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), mannose binding lectin (MBL), and pentraxin 3 (PTX3) which are the mediators and enzymes associated with the inflammatory response to an infectious-inflamed milieu. PS recovered Kp52145-decreased peroxidase (POX), catalase (CAT), complement component 3 (C3), and high-density lipoprotein cholesterol (HDL-C) values. Convergence of ingested plant sterols and host eukaryotic cell-derived defensive lipids mitigates the disruptive effects of bacterial toxic effector molecules. Structural or immunological similarities (molecular mimicry) between ingested plant sterols and host defensive lipids play an important role in modulating bacterial signalling that occurs at the pathogen-host interface and in the mitigation of infection- and inflammation-driven pathological processes.
植物甾醇（PSs）具有抗菌等内在功能。其对宿主介导和细菌介导的发病机制的同时影响尚未完全明确。我们推测，当吸收细胞、防御细胞和解毒细胞共同培养时，它们对感染性病原体的趋同反应取决于摄入的甾醇与其自身防御性脂质之间的分子模拟。建立了包含结肠上皮细胞、巨噬细胞和肝细胞的人类三细胞共培养模型。在纯植物甾醇（β-谷甾醇，PS）存在的情况下，用肺炎克雷伯菌52145（Kp52145）刺激共培养物6小时。测定了受刺激的共培养细胞的结构健康标志物变化及其免疫反应以及致病性的生化标志物。PS显著抑制了Kp52145诱导的细胞因子分泌。与单独的Kp52145组相比，Kp52145 + PS组的细胞活力更高。PS降低了Kp52145诱导的致病性标志物（超氧化物歧化酶，SOD），同时降低了白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、甘露糖结合凝集素（MBL）和五聚素3（PTX3）的水平，这些都是与对感染性炎症环境的炎症反应相关的介质和酶。PS恢复了Kp52145降低的过氧化物酶（POX）、过氧化氢酶（CAT）、补体成分3（C3）和高密度脂蛋白胆固醇（HDL-C）值。摄入的植物甾醇与宿主真核细胞衍生的防御性脂质的趋同减轻了细菌毒性效应分子的破坏作用。摄入的植物甾醇与宿主防御性脂质之间的结构或免疫相似性（分子模拟）在调节病原体-宿主界面发生的细菌信号传导以及减轻感染和炎症驱动的病理过程中发挥着重要作用。
