美他沙酮抑制与疼痛状况相关的炎症细胞因子在小鼠巨噬细胞 RAW264.7 细胞中的产生：与 β-石竹烯的协同作用。
Metaxalone Suppresses Production of Inflammatory Cytokines Associated with Painful Conditions in Mouse Macrophages RAW264.7 Cells : Synergistic Effect with β-caryophyllene.
机构信息
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), 700 Tiverton Avenue, Los Angeles, CA 90095-1732, United States.
Department of Clinical Development, Primus Pharmaceuticals, Inc., Scottsdale, AZ 85251, United States.
出版信息
Curr Mol Med. 2020;20(8):643-652. doi: 10.2174/1566524020666200217102508.
UNLABELLED
Backgrounds and Objective: Inflammation is implicated in the pathogenesis of many diseases. Inflammatory cytokines with painful conditions are well known as biomarkers in human muscle pain, and they are produced by macrophages. Metaxalone is used as a skeletal muscle relaxant, but the mechanism by which metaxalone acts is unknown. This study was undertaken to investigate whether or not metaxalone exhibits an inhibitory effect on the activity of inflammatory macrophages in vitro.
METHODS
Mouse macrophage RAW264.7 cells were cultured in Dulbecco's Modification of Eagle's Medium containing 10% fetal bovine serum in the presence of metaxalone. Cell growth was assayed by counting the number of cells attached to culture dishes. Inflammatory cytokines released into the culture medium were analyzed with the ELISA kit.
RESULTS
Metaxalone (1-100 μM) was found to decrease the number of macrophages by inhibiting the proliferation and stimulating the death of RAW264.7 cells in vitro. The combination of metaxalone (0.1 or 1 μM) and β-caryophyllene (10 or 50 μM), which alone did not have a significant effect on the cell number, caused potential effects on the growth and death of RAW264.7 cells. Mechanistically, molecular levels of mitogenactivated protein kinase were decreased by treatment with metaxalone or β- caryophyllene, and each effect was enhanced by their combination. Furthermore, levels of caspase-3 were increased by metaxalone or β-caryophyllene and enhanced by their combination. Notably, productions of inflammatory cytokines, including tumor necrosis factor-α, interleukin-6 or prostaglandin E2, which were enhanced by lipopolysaccharide (LPS), were repressed by culturing with metaxalone. Levels of cyclooxygenase (COX)-1, COX-2 and nuclear factor kappa B, which were increased by LPS treatment, were reduced by metaxalone.
CONCLUSION
Metaxalone was found to suppress the activity of inflammatory macrophages in vitro.
目的
背景与目的：炎症与许多疾病的发病机制有关。在人类肌肉疼痛中，具有疼痛条件的炎症细胞因子是众所周知的生物标志物，它们由巨噬细胞产生。美索巴莫被用作骨骼肌松弛剂，但美索巴莫的作用机制尚不清楚。本研究旨在探讨美索巴莫是否对体外炎症性巨噬细胞的活性有抑制作用。
方法
在含有 10%胎牛血清的 DMEM 培养基中培养 RAW264.7 细胞，加入美索巴莫。通过计算贴壁培养皿中细胞的数量来检测细胞生长。采用 ELISA 试剂盒分析培养上清液中炎症细胞因子的释放。
结果
美索巴莫（1-100μM）在体外可通过抑制 RAW264.7 细胞的增殖和刺激其死亡来减少巨噬细胞的数量。美索巴莫（0.1 或 1μM）与β-石竹烯（10 或 50μM）联合使用，单独使用时对细胞数量没有显著影响，但对 RAW264.7 细胞的生长和死亡有协同作用。在机制上，美索巴莫或β-石竹烯处理后，丝裂原活化蛋白激酶的分子水平降低，且其协同作用增强。此外，美索巴莫或β-石竹烯增加了 caspase-3 的水平，且其协同作用增强。值得注意的是，美索巴莫抑制了脂多糖（LPS）增强的肿瘤坏死因子-α、白细胞介素-6 或前列腺素 E2 等炎症细胞因子的产生。LPS 处理后 COX-1、COX-2 和核因子 κB 的水平升高，而美索巴莫降低了这些水平。
结论
美索巴莫在体外抑制炎症性巨噬细胞的活性。
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