Li Zhong-Da, Geng Meng-Yu, Dou Song-Rui, Wang Xuan, Zhang Zi-Han, Chang Yan-Zhong
Ministry of Education Key Laboratory of Molecular and Cellular Biology, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, No. 20 Nan'erhuan Eastern Road, Shijiazhuang 050024, China.
Life (Basel). 2022 Jul 10;12(7):1025. doi: 10.3390/life12071025.
Caffeine is well-known as a psychostimulant, and it can also be beneficial in numerous diseases such as diabetes and different types of cancer. Previous studies have shown that caffeine can have a protective role in bacterial infection-induced inflammation and hyperoxia-mediated pulmonary inflammation. Hepcidin, which is regulated by the IL-6/STAT3 inflammation pathway, is a peptide hormone that maintains systemic iron homeostasis. We hypothesized that caffeine's effects on inflammation may also influence hepcidin production and therefore systemic iron metabolism. To this end, we treated 2-month-old mice with caffeine by daily intragastric administration for 7 days, administering intraperitoneal LPS after the final caffeine treatment. Twelve hours after LPS treatment the mice were euthanized, and tissues were collected. We found that caffeine decreased hepatic hepcidin expression and attenuated LPS-induced hepatic hepcidin overexpression. IL-6 expression and STAT3 phosphorylation were also reduced upon caffeine administration. Additionally, hepatic and splenic FPN1 levels increased after caffeine treatment, leading to lower iron levels in liver and spleen tissues and higher iron levels in serum. Caffeine also prevented the increase in spleen weight and decrease in body weight after LPS treatment. Together, our findings suggest that caffeine decreases hepcidin expression via inhibiting inflammation and the activation of the IL-6/STAT3 pathway, thus presenting an attractive, potential therapeutic for the treatment of anemia of inflammation.
咖啡因作为一种精神兴奋剂广为人知，并且它在多种疾病（如糖尿病和不同类型的癌症）中也可能有益。先前的研究表明，咖啡因在细菌感染诱导的炎症和高氧介导的肺部炎症中可发挥保护作用。受白细胞介素-6/信号转导和转录激活因子3（IL-6/STAT3）炎症途径调控的铁调素是一种维持全身铁稳态的肽类激素。我们推测，咖啡因对炎症的影响可能也会影响铁调素的产生，进而影响全身铁代谢。为此，我们对2月龄小鼠每日进行7天的咖啡因灌胃处理，在最后一次咖啡因处理后腹腔注射脂多糖（LPS）。LPS处理12小时后对小鼠实施安乐死并收集组织。我们发现，咖啡因降低了肝脏中铁调素的表达，并减弱了LPS诱导的肝脏铁调素过度表达。给予咖啡因后，白细胞介素-6的表达和信号转导和转录激活因子3的磷酸化也有所降低。此外，咖啡因处理后肝脏和脾脏中铁转运蛋白1（FPN1）水平升高，导致肝脏和脾脏组织中铁水平降低，血清中铁水平升高。咖啡因还预防了LPS处理后脾脏重量的增加和体重的减轻。总之，我们的研究结果表明，咖啡因通过抑制炎症和IL-6/STAT3途径的激活来降低铁调素的表达，从而为炎症性贫血的治疗提供了一种有吸引力的潜在疗法。
