Glucocorticoids increase tissue cell protection against pore-forming toxins from pathogenic bacteria.
Glucocorticoids increase tissue cell protection against pore-forming toxins from pathogenic bacteria.
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DOI：
10.1038/s42003-023-04568-w
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发表时间：
2023-02-17
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
许多种类的致病细菌通过分泌在质膜上形成毛孔的毒素来破坏组织细胞。在这里，我们展示了糖皮质激素增加了组织细胞对毛孔形成毒素的内在保护。地塞米松保护几种细胞类型不受化脓性Trueperella产生的依赖胆固醇的细胞溶血素--溶血素的影响。地塞米松治疗减少了溶血素引起的钾和乳酸脱氢酶的泄漏，限制了肌动蛋白细胞骨架的改变，减少了质膜的起泡，并防止了细胞溶解。氢化可的松和氟替卡松也能保护细胞免受溶血素诱导的细胞损伤。此外，地塞米松还能保护HeLa和A549细胞免受化脓性链球菌的致孔素O和金黄色葡萄球菌的α-溶血素的攻击。地塞米松细胞保护与细胞胆固醇的变化或激活丝裂原活化蛋白激酶(MAPK)细胞应激反应无关。然而，细胞保护依赖于糖皮质激素受体和3-羟基-3-甲基-戊二酰辅酶A还原酶(HMGCR)。总而言之，我们的发现表明，糖皮质激素可以被用来限制由分泌毛孔形成毒素的病原体造成的组织损伤。用糖皮质激素处理细胞系可提供保护，防止随后暴露于选定的细菌形成孔毒素所造成的损害，并依赖于糖皮质激素受体。
Many species of pathogenic bacteria damage tissue cells by secreting toxins that form pores in plasma membranes. Here we show that glucocorticoids increase the intrinsic protection of tissue cells against pore-forming toxins. Dexamethasone protected several cell types against the cholesterol-dependent cytolysin, pyolysin, from Trueperella pyogenes. Dexamethasone treatment reduced pyolysin-induced leakage of potassium and lactate dehydrogenase, limited actin cytoskeleton alterations, reduced plasma membrane blebbing, and prevented cytolysis. Hydrocortisone and fluticasone also protected against pyolysin-induced cell damage. Furthermore, dexamethasone protected HeLa and A549 cells against the pore-forming toxins streptolysin O from Streptococcus pyogenes, and alpha-hemolysin from Staphylococcus aureus. Dexamethasone cytoprotection was not associated with changes in cellular cholesterol or activating mitogen-activated protein kinase (MAPK) cell stress responses. However, cytoprotection was dependent on the glucocorticoid receptor and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR). Collectively, our findings imply that glucocorticoids could be exploited to limit tissue damage caused by pathogens secreting pore-forming toxins. Treating cell lines with glucocorticoids offers protection against the damage caused by subsequent exposure to selected bacterial pore-forming toxins, and is dependent on the glucocorticoid receptor.
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