Jolicoeur C, Lemay A, Akoum A
Laboratoire d'Endocrinologie de la Reproduction, Centre de Recherche, H pital Saint-François, d'Assise, Centre Hospitalier Universitaire de Québec, Université Laval, Canada.
Am J Reprod Immunol. 2001 Feb;45(2):86-93. doi: 10.1111/j.8755-8920.2001.450204.x.
Endometriosis is associated with a chronic inflammatory process, and the increased number of activated peritoneal macrophages is one of the major hallmarks of this process. The medical treatment of the disease, which is based on the creation of an hypoestrogenic milieu unfavorable to the growth of endometriotic lesions, is often associated with a reduced peritoneal inflammation. The aim of this study was to investigate the ability of current therapeutic agents to modulate, through a direct mechanism, the expression by endometriotic cells of monocyte chemotactic protein-1 (MCP-1), a chemokine endowed with the potent faculty of recruiting and activating macrophages.
Cells were stimulated with interleukin-1 beta (IL-1beta) to induce MCP-1 expression. MCP-1 protein secretion and mRNA steady-state levels were evaluated by ELISA and northern blot, respectively.
Our results show that danazol concentrations (10(-7) -10(-5) M), taking into account the therapeutic levels found in the plasma of treated patients, inhibited MCP-1 protein and mRNA steady-state levels in endometriotic cells, whereas buserelin acetate (0.1-10 ng/mL), a GnRH agonist, had no significant effect. Dexamethasone, an anti-inflammatory glucocorticoid, used at concentrations varying between 10(-12) and 10(-6) M, also displayed a dose-dependent inhibitory action.
These results put into prominence the capability of danazol to directly inhibit the expression of a potent monocyte chemotactic and activating factor by ectopic endometrial cells shedding more light on the mechanisms underlying the clinical effects of hormonal therapeutic agents used in the treatment of endometriosis.
子宫内膜异位症与慢性炎症过程相关，活化的腹膜巨噬细胞数量增加是该过程的主要标志之一。基于创造不利于子宫内膜异位病灶生长的低雌激素环境的该疾病的药物治疗，通常与腹膜炎症减轻相关。本研究的目的是调查当前治疗药物通过直接机制调节子宫内膜异位细胞表达单核细胞趋化蛋白-1（MCP-1）的能力，MCP-1是一种具有招募和激活巨噬细胞强大能力的趋化因子。
用白细胞介素-1β（IL-1β）刺激细胞以诱导MCP-1表达。分别通过酶联免疫吸附测定（ELISA）和Northern印迹法评估MCP-1蛋白分泌和mRNA稳态水平。
我们的结果表明，考虑到在接受治疗患者血浆中发现的治疗水平，达那唑浓度（10^-7 - 10^-5 M）可抑制子宫内膜异位细胞中MCP-1蛋白和mRNA稳态水平，而GnRH激动剂醋酸布舍瑞林（0.1 - 10 ng/mL）则无显著影响。抗炎糖皮质激素地塞米松在10^-12至10^-6 M之间的不同浓度下使用时，也表现出剂量依赖性抑制作用。
这些结果突出了达那唑直接抑制异位子宫内膜细胞表达一种强大的单核细胞趋化和激活因子的能力，为用于治疗子宫内膜异位症的激素治疗药物临床效果的潜在机制提供了更多线索。
