Roquette Frères, Rue de la Haute Loge, 62136 Lestrem, France.
ProfileHIT, 7 Rue du Buisson, 44680 Sainte-Pazanne, France.
Int J Mol Sci. 2024 Sep 9;25(17):9748. doi: 10.3390/ijms25179748.
KLEPTOSE CRYSMEB methylated cyclodextrin derivative displays less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases, linked in part to cholesterol complexation and immune response, however, its impact on inflammatory cascade pathways is not clear. Thus, the impact of KLEPTOSE CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells under physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP Diversity PLUS panel. Finally, its anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects that were driven by the inhibition of pro-inflammatory cytokine secretion and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Additionally, it appeared that the mechanism of action of KLEPTOSE CRYSMEB seems to not be shared by other well-known anti-inflammatory molecules. Finally, KLEPTOSE CRYSMEB may have an anti-inflammatory impact, which could be due to its effect on receptors such as TLR or direct complexation with LPS or PGE2, and conversely, this methylated cyclodextrin could stimulate a pro-inflammatory response involving lipid mediators and on proteins involved in communication with immune cells, probably via interaction with membrane cholesterol.
KLEPTOSE CRYSMEB 是一种甲基化环糊精衍生物，其取代的甲基化基团比随机甲基化环糊精少。它已被证明对动脉粥样硬化和神经退行性疾病有影响，部分原因是与胆固醇络合和免疫反应有关，但它对炎症级联途径的影响尚不清楚。因此，在生理和炎症条件下，使用人脐静脉内皮细胞评估了 KLEPTOSE CRYSMEB 对各种药理学靶标的影响，然后使用 BioMAP Diversity PLUS 面板筛选了针对十二个人原代细胞系统的药物，这些系统旨在模拟血管、皮肤、肺和炎症组织的复杂人类组织和疾病生物学。最后，在体外研究了其抗炎机制，以评估其抗炎或促解决特性。结果表明，KLEPTOSE CRYSMEB 可以调节免疫系统，并通过刺激参与免疫细胞与其他细胞类型之间串扰的分子的表达，潜在地管理血管问题。它显示出抗炎作用，其驱动力是抑制促炎细胞因子的分泌，并可能对不同的组织类型产生不同的影响。此外，这种环糊精对促解决脂质介质没有明显的影响。此外，KLEPTOSE CRYSMEB 的作用机制似乎与其他知名抗炎分子不同。最后，KLEPTOSE CRYSMEB 可能具有抗炎作用，这可能是由于其对 TLR 等受体的作用，或直接与 LPS 或 PGE2 络合，相反，这种甲基化环糊精可能会刺激涉及脂质介质和与免疫细胞通讯的蛋白质的促炎反应，可能通过与膜胆固醇相互作用。
