Department of Neurology, Ghent University and Ghent University Hospital, 9000 Ghent, Belgium.
Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany.
Int J Mol Sci. 2022 Aug 24;23(17):9567. doi: 10.3390/ijms23179567.
Duchenne Muscular Dystrophy (DMD) is a debilitating muscle disorder that condemns patients to year-long dependency on glucocorticoids. Chronic glucocorticoid use elicits many unfavourable side-effects without offering satisfying clinical improvement, thus, the search for alternative treatments to alleviate muscle inflammation persists. Taurine, an osmolyte with anti-inflammatory effects, mitigated pathological features in the mouse model for DMD but interfered with murine development. In this study, ectoine is evaluated as an alternative for taurine in vitro in CCL-136 cells and in vivo in the mouse. Pre-treating CCL-136 cells with 0.1 mM taurine and 0.1 mM ectoine prior to exposure with 300 U/mL IFN-γ and 20 ng/mL IL-1β partially attenuated cell death, whilst 100 mM taurine reduced MHC-I protein levels. In vivo, histopathological features of the tibialis anterior in mice were mitigated by ectoine, but not by taurine. Osmolyte treatment significantly reduced mRNA levels of inflammatory disease biomarkers, respectively, CCL2 and SPP1 in ectoine-treated mice, and CCL2, HSPA1A, TNF-α and IL-1β in taurine-treated mice. Functional performance was not improved by osmolyte treatment. Furthermore, ectoine-treated mice exhibited reduced body weight. Our results confirmed beneficial effects of taurine in mice and, for the first time, demonstrated similar and differential effects of ectoine.
杜氏肌营养不良症（DMD）是一种使人衰弱的肌肉疾病，会使患者在一年内依赖于糖皮质激素。慢性糖皮质激素的使用会引起许多不良的副作用，而不会带来令人满意的临床改善，因此，寻找替代治疗方法来缓解肌肉炎症的需求仍然存在。牛磺酸是一种具有抗炎作用的渗透剂，可减轻 DMD 小鼠模型中的病理特征，但会干扰小鼠的发育。在这项研究中，我们评估了作为牛磺酸替代物的 4-羟乙基哌嗪乙磺酸（ectoine）在体外的 CCL-136 细胞中和体内的 小鼠中的作用。在暴露于 300 U/mL IFN-γ和 20 ng/mL IL-1β之前，用 0.1 mM 牛磺酸和 0.1 mM ectoine 预处理 CCL-136 细胞可部分减轻细胞死亡，而 100 mM 牛磺酸可降低 MHC-I 蛋白水平。在体内，ectoine 可减轻 小鼠前胫骨肌的组织病理学特征，但牛磺酸不行。渗透调节剂治疗可分别显著降低 ectoine 治疗的 小鼠中炎症疾病生物标志物 CCL2 和 SPP1 的 mRNA 水平，以及牛磺酸治疗的 小鼠中 CCL2、HSPA1A、TNF-α和 IL-1β的 mRNA 水平。渗透调节剂治疗并未改善功能表现。此外，ectoine 治疗的 小鼠体重减轻。我们的研究结果证实了牛磺酸对 小鼠的有益作用，并首次证明了 4-羟乙基哌嗪乙磺酸的相似和不同作用。
