Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
Cells. 2022 Dec 1;11(23):3886. doi: 10.3390/cells11233886.
Recent studies have suggested that mouse cathelicidin-related antimicrobial peptide (CRAMP) and its human homologue leucine leucine-37 (LL-37) play critical roles in innate immune responses. Here, we studied the role of mouse CRAMP in bacterial endotoxin lipopolysaccharide (LPS)-induced neuroinflammation. CRAMP peptide treatment significantly inhibited LPS-mediated inflammatory activation of glial cells in culture. In the animal model of LPS-induced neuroinflammation, CRAMP expression was highly induced in multiple cell types, such as astrocytes, microglia, and neurons. Injection of exogenous CRAMP peptide significantly inhibited inflammatory cytokine expression and the reactivity of glial cells in the mouse brain following intraperitoneal or intracerebroventricular LPS administration. Altogether, results of the study suggest that CRAMP plays an important part in containment of LPS-induced neuroinflammatory responses, and that CRAMP can be exploited for the development of targeted therapies for neuroinflammatory conditions associated with bacterial infection.
最近的研究表明，鼠抗菌肽相关 cathelicidin（CRAMP）及其人类同源物亮氨酸亮氨酸-37（LL-37）在先天免疫反应中发挥着关键作用。在这里，我们研究了鼠 CRAMP 在细菌内毒素脂多糖（LPS）诱导的神经炎症中的作用。CRAMP 肽处理显著抑制了培养中的神经胶质细胞中 LPS 介导的炎症激活。在 LPS 诱导的神经炎症动物模型中，CRAMP 表达在多种细胞类型中被高度诱导，如星形胶质细胞、小胶质细胞和神经元。腹腔内或侧脑室给予外源性 CRAMP 肽后，明显抑制了炎性细胞因子的表达和小鼠大脑中神经胶质细胞的反应性。综上所述，研究结果表明，CRAMP 在控制 LPS 诱导的神经炎症反应中起着重要作用，并且可以利用 CRAMP 开发针对与细菌感染相关的神经炎症的靶向治疗方法。
