Increased vascular endothelial cell production of interleukin-6 in severe preeclampsia

OBJECTIVE: The purpose of this study was to determine whether plasma from women with severe preeclampsia stimulates the production of endothelial cell interleukin-6 production and whether vitamin E could inhibit this process. STUDY DESIGN: Human umbilical vein endothelial cells were cultured in the presence of 5% plasma from women with severe preeclampsia (n = 12) or healthy pregnant women at term (n = 12), with or without 50 micromol/L vitamin E. Levels of interleukin-6 in plasma and human umbilical vein endothelial cell-conditioned media were measured by enzyme-linked immunosorbent assay. RESULTS: Interleukin-6 levels were elevated 5-fold in preeclamptic plasma compared with normal pregnant plasma (P <.05). Human umbilical vein endothelial cell interleukin-6 production was increased 25% by preeclamptic plasma compared with normal pregnant plasma (P <.005), and increased interleukin-6 production by preeclamptic plasma was inhibited by vitamin E. CONCLUSION: Endothelial cell activation by preeclamptic plasma stimulates interleukin-6 production, which is inhibited by vitamin E. These findings provide a potential cellular mechanism for the beneficial effects of antioxidant therapy in preeclampsia.     

Induction of circulating monocyte chemoattractant protein-1 in women with gonadotropin-releasing hormone agonist

The aim of the present study was to determine the influence of acute estrogen deficiency induced by administration of a gonadotropin-releasing hormone (GnRH) agonist on circulating levels of cytokines and chemokines. Eighty-three women with uterine leiomyoma were assigned in open, parallel-group fashion to a no-treatment (control) group and a GnRH-agonist group. Serum levels of nine cytokines and chemokines as well as vascular inflammatory markers were measured. Serum levels of monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor-α (TNFα) in the GnRH-agonist group were increased significantly at 6 months. There were also significant differences in percentage changes in interleukin (IL)-6, IL8, MCP1, and macrophage inflammatory protein-1β (MIP1β) between the control and GnRH agonist groups. Soluble intercellular adhesion molecule-1 (sICAM1) and E-selectin levels showed significant increases in the GnRH agonist group at 6 months. Serum MCP1 concentrations showed weak correlations with levels of sICAM and E-selectin. We conclude that a hypo-estrogenic state due to administration of a GnRH agonist increases circulating levels of cytokines and chemokines, especially MCP1.     

Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1

Purpose

The objective of this study was to test the hypothesis that ovarian kisspeptin (kiss1) and its receptor (kiss1r) expression are affected by age, obesity, and the age- and obesity-related chemokine monocyte chemoattractant protein-1 (MCP-1).

Methods

Ovaries from reproductive-aged and older C57BL/6J mice fed normal chow (NC) or high-fat (HF) diet, ovaries from age-matched young MCP-1 knockout and young control mice on NC, and finally, cumulus and mural granulosa cells (GCs) from women who underwent in vitro fertilization (IVF) were collected. Kiss1, kiss1r, anti-Mullerian hormone (AMH), and AMH receptor (AMHR-II) messenger RNA (mRNA) expression levels were quantified using real-time polymerase chain reaction (RT-PCR).

Results

In mouse ovaries, kiss1 and kiss1r mRNA levels were significantly higher in old compared to reproductive-aged mice, and diet-induced obesity did not alter kiss1 or kiss1r mRNA levels. Compared to young control mice, young MCP-1 knockout mice had significantly lower ovarian kiss1 mRNA but significantly higher AMH and AMHR-II mRNA levels. In human cumulus GCs, kiss1r mRNA levels were positively correlated with age but not with BMI. There was no expression of kiss1 mRNA in either cumulus or mural GCs.

Conclusion

These data suggest a possible age-related physiologic role for the kisspeptinergic system in ovarian physiology. Additionally, the inflammatory MCP-1 may be associated with kiss1 and AMH genes, which are important in ovulation and folliculogenesis, respectively.

     

Effect of monocyte chemoattractant protein-1 and estradiol on the secretion of vascular endothelial growth factor in endometrial stromal cells in vitro

To explore the initial activity of endometrial stromal cells (ESCs) and the participation of monocyte chemoattractant protein-1 (MCP-1) in the histogenesis of endometriosis, vascular endothelial growth factor (VEGF) secretion of ESCs and the effect of MCP-1 on VEGF secretion of ESCs were observed in vitro. The VEGF level was detected in ESC culture media and was increased significantly when E2 or MCP-1 was added to the media, especially in the presence of E2 plus MCP-1. The VEGF secretion was higher in the ESCs of women with endometriosis than in those women without endometriosis.     

Increased monocyte chemotactic protein-1 level and activity in the peripheral blood of women with endometriosis

OBJECTIVE: Our purpose was to evaluate monocyte chemotactic protein-1 in the peripheral blood of women with and without endometriosis. STUDY DESIGN: Fifty-seven patients with endometriosis at laparoscopy done for infertility and pelvic pain were compared with 44 fertile women with no evidence of endometriosis at tubal ligation by laparoscopy. Monocyte chemotactic protein-1 concentration in the plasma was determined by enzyme-linked immunosorbent assay and its biologic activity was evaluated by measuring monocyte chemotaxis with use of a human histiocytic cell line (U937). RESULTS: Monocyte chemotactic protein-1 concentrations (median and range of values) found in the plasma were higher in patients with endometriosis (163, 0 to 788 pg/ml) than in normal controls (0, 0 to 355 pg/ml). This elevation was significant only in the minimal stage of endometriosis (revised American Fertility Society stage I). However, increased chemotactic activity (mean number of migrating cells/mm² ± SEM) was found in the stages I (1240 ± 141), II (519 ± 30), and III-IV (523 ± 23) of the disease compared with normal controls (205 ± 20). A total of 35% to 44% of this activity was inhibited in the presence of an antibody specific to monocyte chemotactic protein-1. CONCLUSION: Endometriosis is associated with increased level and activity of monocyte chemotactic protein-1 in the peripheral blood. The elevation and activation of this cytokine could play a relevant role in the immunoinflammatory process associated with the disease. (Am J Obstet Gynecol 1996;175:1620-5.)     

子宫内膜异位症患者腹腔液及异位内膜组织中单核细胞趋化蛋白-1水平与疾病发生关系的研究

目的　探讨单核细胞趋化蛋白 1(MCP 1)在子宫内膜异位症 (EMT)发病中的作用。方法　 2 0 0 1年12月至 2 0 0 3年 1月中国医科大学附属二院采用ELISA法检测盆腔EMT患者腹腔液及异位内膜组织中MCP 1水平 ,探讨EMT分期与MCP 1表达的关系。结果　EMT患者腹腔液MCP 1水平 [(34 0 1± 17 4 0 )ng/L]及异位内膜组织中MCP 1水平 [(92 34± 4 9 4 3)ng/ g·蛋白 ]均较对照组显著增高 ,差异有显著性意义 (P均 <0 0 1) ,MCP 1在疾病早期较晚期明显增高。结论　MCP 1主要参与EMT疾病的早期形成 ,MCP 1是与EMT病理生理机制相关的细胞介质。     

单核细胞趋化蛋白-1在异位内膜组织中的表达

目的 :探讨单核细胞趋化蛋白 1(MCP 1)在子宫内膜异位症发生发展中的作用。方法 :采用免疫组织化学链酶亲和素 生物素 过氧化酶复合物染色法 (SABC法 )及电子计算机图象分析技术 ,分析 2 0例子宫内膜异位症患者的异位内膜与在位内膜中MCP 1的表达 ,并以 2 0例正常子宫内膜作对照组。结果 :MCP 1分布在子宫内膜腺上皮和间质细胞的细胞质中 ,且在腺上皮中的表达高于间质 (P <0 .0 1) ,与月经周期无关。子宫内膜异位症异位内膜与在位内膜中MCP 1呈高表达状态 ,与正常内膜相比 ,差异有高度显著性 (P <0 .0 1)。而在位内膜与异位内膜之间差异亦有高度显著性 (P <0 .0 1)。结论 :MCP 1可能在子宫内膜异位症的发生发展中起重要作用     

宫颈扩张过程中单核细胞趋化蛋白-1表达的意义

目的:观察单核细胞趋化蛋白-1(MCP-1)在分娩期宫颈扩张不同程度时母血、子宫肌层组织和胎盘组织中的表达,探讨MCP-1在宫颈扩张过程中的作用。方法:选择临产后急诊行剖宫产终止妊娠的初产妇42例,根据术前30min宫颈扩张程度分为A组10例(宫颈口开大<2cm),B组10例(宫颈口开大2~4cm),C组10例(宫颈口开大4~6cm),D组12例(宫颈口开大>6cm)。酶联免疫吸附法测定产妇血清中MCP-1水平;用半定量RT-PCR法测定子宫下段肌层及胎盘组织中MCP-1mRNA的表达。结果:C组和D组血清MCP-1水平和组织中MCP-1mRNA含量显著高于A组和B组(P<0.01),B组组织中MCP-1mRNA含量显著高于A组(P<0.05);4组产妇MCP-1的表达量与宫颈扩张程度呈正相关。结论:MCP-1在宫颈扩张过程中表达增加,在宫颈扩张过程中起重要作用。     

离体异位子宫内膜细胞中单核细胞趋化蛋白-1的测定

目的　探讨异位子宫内膜细胞产生单核细胞趋化蛋白１（ＭＣＰ１）的临床意义。方法　收集１５ 例子宫内膜异位症患者的异位内膜组织进行体外细胞培养,分别加入纯培养液（ 对照组） 、含白细胞介素１β（ＩＬ１β）２ ｎｇ／ｍｌ（ＩＬ１β诱导组）及肿瘤坏死因子α（ＴＮＦα）２０ ｍｇ／ｍｌ（ＴＮＦα诱导组）的培养液培养４ 小时,应用斑点杂交、免疫组织化学及夹心酶联免疫吸附试验检测各组异位细胞中ＭＣＰ１ｍＲＮＡ蛋白的表达水平及其培养上清中ＭＣＰ１ 的含量。结果　与对照组相比,异位内膜细胞经ＩＬ１β及ＴＮＦα作用后表达的ＭＣＰ１ ｍＲＮＡ和蛋白水平显著增加（ Ｐ＜ ０．０１ ,Ｐ＜０．０５）;培养上清中ＭＣＰ１ 的含量也显著增加（Ｐ＜０ ．０１ ,Ｐ＜ ０．０５）。结论　ＩＬ１β及ＴＮＦα可刺激异位内膜细胞中ＭＣＰ１ 的表达显著增加,这可能和子宫内膜异位症的病变发展有关。     

Fluvastatin reduces oxidative stress, decreases serum monocyte chemotactic protein-1 level and improves endothelial function in patients with hypercholesterolemia.

BACKGROUND AND PURPOSE: Statins may have anti-inflammatory properties and exert endothelial protection independently of their lipid-lowering effect. However, data are scarce concerning the co-existence of these lipid-lowering-independent effects in humans. METHODS: Forty three patients with hypercholesterolemia were randomly assigned in a 2:1 ratio to receive either fluvastatin 80 mg/day (n = 30) or placebo (n = 13) for 12 weeks. Plasma levels of monocyte chemotactic protein-1 (MCP-1), thiobarbituric acid reactive substances (TBARS)--an index of oxidative stress, and flow-mediated vasodilatation (FMD)--an index of endothelial function, were measured before and after statin therapy. RESULTS: Fluvastatin significantly reduced the serum level of total cholesterol (201.8 +/- 25.2 vs 271.6 +/- 24.7 mg/dL; p < 0.001), low-density lipoprotein cholesterol (129.4 +/- 5.1 vs 190.2 +/- 19 mg/dL; p < 0.001), MCP-1 (190.3 +/- 40 vs 217.6 +/- 61 pg/mL; p = 0.001), and TBARS (3.7 +/- 1.3 vs 5.2 +/- 1.4 nmol/mL; p < 0.001). FMD was significantly increased, from 3.7 +/- 2.5% to 5.9 +/- 2.9% (p < 0.001) in the fluvastatin group. The reduction of serum MCP-1 or TBARS level was not correlated with the improvement of either plasma cholesterol level or FMD. No significant changes of these markers were observed in the placebo group. CONCLUSIONS: Fluvastatin reduced oxidative stress and inflammatory marker levels, and improved endothelial function, in addition to its lipid-lowering effect. These observations provide a clinical rationale for the co-existence of complex and multiple vascular protective mechanisms of statins.