Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk.
Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk.
复制标题
DOI：
10.1210/en.2017-00562
复制
发表时间：
2018-01-01
期刊：
影响因子：
4.8
通讯作者：
Korach KS
中科院分区：
文献类型：
--
作者：
Burns KA;Thomas SY;Hamilton KJ;Young SL;Cook DN;Korach KS
子宫内膜异位症是一种妇科疾病，对十分之一的妇女的健康产生负面影响。尽管人们对晚期疾病了解更多，但对子宫内膜异位症的早期启动和病变发展知之甚少。在此，我们使用子宫内膜异位症的子宫组织移植小鼠模型来检查疾病的早期发展及其在疾病开始的72小时内对雌二醇（E2）和雌激素受体（ER）α的依赖性。使用野生型和ERα敲除小鼠作为宿主或供体，我们发现大量中性粒细胞和巨噬细胞浸润到腹腔中。通过检测细胞浸润、病变基因表达和腹腔液，我们发现E2/ERα在早期病变发展中起次要作用。免疫介导的信号传导主导E2介导的信号传导，但在疾病开始后48小时，在缺乏ERα的病变中发现白细胞介素（IL）-6介导的反应减弱。我们的数据提供了证据表明，子宫内膜异位症的早期启动主要依赖于免疫系统，而E2/ERα/IL-6介导的串扰起部分作用。这些研究结果表明，有两个阶段的乳腺癌-免疫依赖性阶段和乳腺癌依赖性阶段，并针对先天免疫系统可以防止病变附着在这个易感人群的妇女。子宫内膜异位症的小鼠模型，用于检查疾病的早期启动，揭示了疾病存在两个阶段-免疫为主阶段和免疫为主阶段。
Endometriosis is a gynecological disease that negatively affects the health of 1 in 10 women. Although more information is known about late stage disease, the early initiation of endometriosis and lesion development is poorly understood. Herein, we use a uterine tissue transfer mouse model of endometriosis to examine early disease development and its dependence on estradiol (E2) and estrogen receptor (ER) α within 72 hours of disease initiation. Using wild-type and ERα knockout mice as hosts or donors, we find substantial infiltration of neutrophils and macrophages into the peritoneal cavity. Examining cell infiltration, lesion gene expression, and peritoneal fluid, we find that E2/ERα plays a minor role in early lesion development. Immune-mediated signaling predominates E2-mediated signaling, but 48 hours after the initiation of disease, a blunted interleukin (IL)-6-mediated response is found in developing lesions lacking ERα. Our data provide evidence that the early initiation of endometriosis is predominantly dependent on the immune system, whereas E2/ERα/IL-6-mediated cross-talk plays a partial role. These findings suggest there are two phases of endometriosis—an immune-dependent phase and a hormone-dependent phase, and that targeting the innate immune system could prevent lesion attachment in this susceptible population of women. A mouse model of endometriosis, used to examine the early initiation of disease, revealed that two phases of disease exist—an immune-predominant phase and hormone-predominant phase.
登录
查看更多内容
影响因子：
64.5
作者：
Han SJ;Jung SY;Wu SP;Hawkins SM;Park MJ;Kyo S;Qin J;Lydon JP;Tsai SY;Tsai MJ;DeMayo FJ;O'Malley BW
通讯作者：
O'Malley BW
影响因子：
20.3
作者：
Christoffersson, Gustaf;Vagesjo, Evelina;Phillipson, Mia
通讯作者：
Phillipson, Mia
DOI：
10.1530/rep-16-0052
发表时间：
2016-09
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Greene AD;Lang SA;Kendziorski JA;Sroga-Rios JM;Herzog TJ;Burns KA
通讯作者：
Burns KA
影响因子：
20.3
作者：
Fantin, Alessandro;Vieira, Joaquim M.;Ruhrberg, Christiana
通讯作者：
Ruhrberg, Christiana
影响因子：
4.3
作者：
DHooghe, TM;Bambra, CS;Koninckx, PR
通讯作者：
Koninckx, PR