Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Orthopaedics, The Fifth Affiliated Hospital, Southerm Medical University, Guangzhou, China.
Int Immunopharmacol. 2024 Jun 30;135:112223. doi: 10.1016/j.intimp.2024.112223. Epub 2024 May 20.
Although smoking is a significant risk factor for osteomyelitis, there is limited experimental evidence that nicotine, a key tobacco constituent, is associated with this condition, leaving its mechanistic implications uncharacterized. This study revealed that nicotine promotes Staphylococcus aureus-induced osteomyelitis by increasing Nrf2 and Slc7a11 expression in vivo and in vitro. Inhibition of Slc7a11 using Erastin augmented bacterial phagocytosis/killing capabilities and fortified antimicrobial responses in an osteomyelitis model. Moreover, untargeted metabolomic analysis demonstrated that Erastin mitigated the effects of nicotine on S. aureus-induced osteomyelitis by altering glutamate/glutathione metabolism. These findings suggest that nicotine aggravates S. aureus-induced osteomyelitis by activating the Nrf2/Slc7a11 signaling pathway and that Slc7a11 inhibition can counteract the detrimental health effects of nicotine.
尽管吸烟是骨髓炎的一个重要危险因素，但有限的实验证据表明，尼古丁是烟草的主要成分之一，与这种疾病有关，其机制影响尚不清楚。本研究表明，尼古丁通过体内和体外增加 Nrf2 和 Slc7a11 的表达来促进金黄色葡萄球菌引起的骨髓炎。使用 Erastin 抑制 Slc7a11 增强了金黄色葡萄球菌感染模型中的细菌吞噬/杀伤能力和增强了抗菌反应。此外，非靶向代谢组学分析表明，Erastin 通过改变谷氨酸/谷胱甘肽代谢来减轻尼古丁对金黄色葡萄球菌诱导的骨髓炎的影响。这些发现表明，尼古丁通过激活 Nrf2/Slc7a11 信号通路加重金黄色葡萄球菌诱导的骨髓炎，而 Slc7a11 抑制可以抵消尼古丁对健康的有害影响。
