Interleukin-33 modulates inflammation in endometriosis.
Interleukin-33 modulates inflammation in endometriosis.
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DOI：
10.1038/s41598-017-18224-x
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发表时间：
2017-12-20
影响因子：
4.6
通讯作者：
Tayade C
中科院分区：
文献类型：
--
作者：
Miller JE;Monsanto SP;Ahn SH;Khalaj K;Fazleabas AT;Young SL;Lessey BA;Koti M;Tayade C
子宫内膜异位症是一种使人衰弱的疾病，其分类为子宫内膜组织在子宫外的异常生长。虽然这种疾病的发病机制尚不清楚，它是公认的，子宫内膜异位症患者表现出免疫功能障碍。白细胞介素（IL）-33是一种危险信号，是慢性炎症的关键调节因子。虽然血浆和腹腔液中IL-33水平与深部浸润性子宫内膜异位症有关，但其对疾病病理生理的作用尚不清楚。我们使用患者样本、细胞系和同基因小鼠模型研究了IL-33在子宫内膜异位症病理学中的作用。我们发现，子宫内膜异位症病变产生的IL-33水平显着高于健康，生育对照组的子宫内膜。在体外用IL-33刺激子宫内膜上皮细胞、内皮细胞和增生性上皮细胞导致促炎细胞因子和血管生成细胞因子的产生。在子宫内膜异位症的同基因小鼠模型中，IL-33注射引起全身炎症，其表现为与对照小鼠相比血浆促炎细胞因子的增加。此外，来自IL-33处理的小鼠的增生性病变高度血管化并表现出增加的增殖。总的来说，我们提供了令人信服的证据表明IL-33使炎症、血管生成和病变增殖持续存在，这些是子宫内膜异位症病变生存和进展的关键事件。
Endometriosis is a debilitating condition that is categorized by the abnormal growth of endometrial tissue outside the uterus. Although the pathogenesis of this disease remains unknown, it is well established that endometriosis patients exhibit immune dysfunction. Interleukin (IL)-33 is a danger signal that is a critical regulator of chronic inflammation. Although plasma and peritoneal fluid levels of IL-33 have been associated with deep infiltrating endometriosis, its contribution to the disease pathophysiology is unknown. We investigated the role of IL-33 in the pathology of endometriosis using patient samples, cell lines and a syngeneic mouse model. We found that endometriotic lesions produce significantly higher levels of IL-33 compared to the endometrium of healthy, fertile controls. In vitro stimulation of endometrial epithelial, endothelial and endometriotic epithelial cells with IL-33 led to the production of pro-inflammatory and angiogenic cytokines. In a syngeneic mouse model of endometriosis, IL-33 injections caused systemic inflammation, which manifested as an increase in plasma pro-inflammatory cytokines compared to control mice. Furthermore, endometriotic lesions from IL-33 treated mice were highly vascularized and exhibited increased proliferation. Collectively, we provide convincing evidence that IL-33 perpetuates inflammation, angiogenesis and lesion proliferation, which are critical events in the lesion survival and progression of endometriosis.
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影响因子：
17.1
作者：
Beste MT;Pfäffle-Doyle N;Prentice EA;Morris SN;Lauffenburger DA;Isaacson KB;Griffith LG
通讯作者：
Griffith LG
DOI：
10.1073/pnas.0703451104
发表时间：
2007-07-24
影响因子：
11.1
作者：
Hever, Aniko;Roth, Richard B.;Ziotnik, Albert
通讯作者：
Ziotnik, Albert
影响因子：
6.1
作者：
Kwak, JY;Park, SW;Lee, KS
通讯作者：
Lee, KS
影响因子：
3.7
作者：
Ahmed, Ammad;Koma, Mousa Komai
通讯作者：
Koma, Mousa Komai
影响因子：
30.5
作者：
Brint, EK;Xu, DM;Liew, FY
通讯作者：
Liew, FY