National Institutes of Health, NIDCR, ASCS, Bethesda, MD, USA.
Department of Neuroradiology, University Hospital Zürich, Zürich, Switzerland.
Sci Rep. 2024 Feb 17;14(1):3986. doi: 10.1038/s41598-024-54227-1.
Bone marrow stromal cells (BMSCs) have immunomodulatory activities in numerous species and have been used in clinical trials. BMSCs also make antibacterial agents. Since hepcidin is known to have antimicrobial effects in fish, we wondered if it might also be used as an antimicrobial agent by mammalian BMSCs. In the present study, we show hepcidin expression in both mouse (mBMSC) and human BMSCs (hBMSC). We observed a hBMSC hepcidin-dependent degradation of ferroportin in HEK-293 reporter cells in vitro. In human and mouse bone marrows (BM) we detected hepcidin-positive BMSCs in close proximity to hematopoietic progenitors. The conditioned culture medium of hBMSCs significantly reduced bacterial proliferation that was partially blocked by a hepcidin-neutralizing antibody. Similarly, medium in which hepcidin-deficient (Hamp) mouse BMSCs had been grown was significantly less effective in reducing bacterial counts than the medium of wild-type cells. In a zymosan-induced peritonitis mouse model we found that mBMSC-derived hepcidin reduced the number of invading polymorphonuclear (PMN) cells in the peritoneal cavity. Our results show that BMSC-derived hepcidin has antimicrobial properties in vitro and also reduces inflammation in vivo. We conclude that hepcidin should be added to the expanding arsenal of agents available to BMSCs to fight infections and inflammation.
骨髓基质细胞（BMSCs）在许多物种中具有免疫调节活性，并已在临床试验中得到应用。BMSCs 还可以产生抗菌剂。由于已知铁调素在鱼类中具有抗菌作用，我们想知道它是否也可以被哺乳动物 BMSCs 用作抗菌剂。在本研究中，我们显示了鼠（mBMSC）和人骨髓基质细胞（hBMSC）中均有铁调素表达。我们观察到 hBMSC 在体外 HEK-293 报告细胞中依赖铁调素的铁蛋白降解。在人骨髓和鼠骨髓中，我们在造血祖细胞附近检测到铁调素阳性的 BMSCs。hBMSC 的条件培养基显著降低了细菌增殖，而铁调素中和抗体部分阻断了这种作用。同样，在生长铁调素缺陷（Hamp）鼠 BMSCs 的培养基中，细菌计数的减少明显低于野生型细胞的培养基。在酵母聚糖诱导的腹膜炎小鼠模型中，我们发现 mBMSC 衍生的铁调素减少了腹腔中入侵的多形核（PMN）细胞的数量。我们的研究结果表明，BMSC 衍生的铁调素有体外抗菌特性，也能减轻体内炎症。我们得出结论，铁调素应该被添加到 BMSCs 可用的不断扩大的抗感染和炎症的武器库中。
