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首页> 外文期刊>IBRO Reports >Therapeutic innovation: Inflammatory-reactive astrocytes as targets of inflammation
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Therapeutic innovation: Inflammatory-reactive astrocytes as targets of inflammation

机译：治疗创新：炎症反应性星形胶质细胞作为炎症的靶标

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This study aimed to test pharmaceutical compounds targeting astrocytes showing inflammatory dysregulation. The primary rat brain cultures were treated with different batches of serum with or without microglia added to make the cells inflammatory-reactive. Lipopolysaccharide (LPS) and tryptase were used as inflammatory inducers. Expression levels of Toll-like receptor 4 (TLR4), Na + /K + -ATPase, and matrix metalloprotease-13 (MMP-13), as well as actin filament organization, pro-inflammatory cytokines, and intracellular Ca 2+ release, were evaluated. LPS combined with tryptase upregulated TLR4 expression, whereas Na + /K + -ATPase expression was downregulated, ATP-evoked Ca 2+ transients were increased, actin filaments were reorganized and ring structures instead of stress fibers were observed. Other aims of the study were to prevent astrocytes from becoming inflammatory-reactive and to restore inflammatory dysregulated cellular changes. A combination of the μ-opioid antagonist (?)-naloxone in ultra-low concentrations, the non-addictive μ-opioid agonist (?)-linalool, and the anti-epileptic agent levetiracetam was examined. The results indicated that this drug cocktail prevented the LPS- and tryptase-induced inflammatory dysregulation. The drug cocktail could also restore the LPS- and tryptase-treated cells back to a normal physiological level in terms of the analyzed parameters. Highlights ? New combinations of pharmaceutical compounds can resolve and restore disordered cellular inflammatory pathways in network coupled cells. ? Gap junctions coupled cells may be targets of inflammation. ? The new combination has been tested using in?vitro networks of astrocytes. ? Clinical consequences of chronic inflammation in one or several organs are increased risks for co-morbidity seen in several diseases.
机译：这项研究旨在测试靶向星形胶质细胞的药物化合物，该化合物显示出炎症失调。用不同批次的血清处理原代大鼠脑培养物，添加或不添加小胶质细胞，使细胞发生炎症反应。脂多糖（LPS）和类胰蛋白酶被用作炎症诱导剂。 Toll样受体4（TLR4），Na + / K + -ATPase和基质金属蛋白酶13（MMP-13）的表达水平，以及肌动蛋白丝组织，促炎细胞因子和细胞内Ca 2+释放，被评估。 LPS结合类胰蛋白酶上调了TLR4的表达，而Na + / K + -ATPase的表达下调，ATP诱发的Ca 2+瞬变增加，肌动蛋白丝重新组织，并观察到了环状结构而不是应力纤维。该研究的其他目的是防止星形胶质细胞发生炎症反应，并恢复炎症失调的细胞变化。研究了超低浓度的μ阿片拮抗剂（α）-纳洛酮，非成瘾性μ阿片激动剂（α）-芳樟醇和抗癫痫药左乙拉西坦的组合。结果表明，这种药物混合物可预防LPS和类胰蛋白酶引起的炎症失调。就所分析的参数而言，药物混合物还可以将经LPS和胰蛋白酶处理的细胞恢复至正常的生理水平。强调 ？药物化合物的新组合可以解决和恢复网络耦合细胞中紊乱的细胞炎症途径。 ？间隙连接偶联的细胞可能是炎症的目标。 ？新的组合已经使用星形胶质细胞体外网络进行了测试。 ？一个或多个器官中慢性炎症的临床后果是几种疾病中合并症的风险增加。

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