Bottles K D, Morrissey J H
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Blood Coagul Fibrinolysis. 1993 Jun;4(3):405-14. doi: 10.1097/00001721-199306000-00002.
Stimulation of monocytic cells by inflammatory agents such as bacterial lipopolysaccharide or tumour necrosis factor-alpha leads to the rapid and transient expression of tissue factor, the major cellular initiator of the extrinsic coagulation cascade in both haemostasis and tissue inflammation. In this study we investigated whether the synthetic anti-inflammatory glucocorticoid, dexamethasone, would inhibit agonist induction of tissue factor expression in both monocytes and endothelial cells. Surprisingly, dexamethasone significantly enhanced the induction of tissue factor expression by peripheral blood mononuclear cells and an established monocytic cell line, THP-1, in response to lipopolysaccharide or tumour necrosis factor-alpha. However, unlike monocytic cells, dexamethasone did not enhance agonist induction of tissue factor in endothelial cells. Synergistic enhancement of tissue factor expression by dexamethasone was also reflected in tissue factor mRNA levels in THP-1 cells, but was not the result of improved TF mRNA stability. Synergism between bacterial lipopolysaccharide and glucocorticoid in the induction of monocyte effector function is extremely unusual and may help to explain the variable outcome of glucocorticoid treatment of septic shock.
诸如细菌脂多糖或肿瘤坏死因子-α等炎性介质刺激单核细胞会导致组织因子快速短暂表达，组织因子是止血和组织炎症中外源性凝血级联反应的主要细胞启动因子。在本研究中，我们调查了合成抗炎糖皮质激素地塞米松是否会抑制单核细胞和内皮细胞中激动剂诱导的组织因子表达。令人惊讶的是，地塞米松显著增强了外周血单核细胞和已建立的单核细胞系THP-1对脂多糖或肿瘤坏死因子-α的反应中组织因子表达的诱导。然而，与单核细胞不同，地塞米松并未增强内皮细胞中激动剂诱导的组织因子表达。地塞米松对组织因子表达的协同增强也反映在THP-1细胞中的组织因子mRNA水平上，但并非TF mRNA稳定性提高的结果。细菌脂多糖和糖皮质激素在诱导单核细胞效应功能方面的协同作用极为罕见，可能有助于解释糖皮质激素治疗脓毒性休克的不同结果。
