Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology.
Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology.
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DOI：
10.3389/fimmu.2022.961599
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
子宫内膜异位症是一种雌激素依赖性慢性炎症性疾病，其特征是子宫内膜在子宫外生长。肥大细胞不仅在调节过敏反应中，而且在调节其他机制如血管生成、纤维化和疼痛中也起着关键作用。雌激素对肥大细胞功能的影响也被认为是许多过敏性和慢性炎症性疾病中驱动疾病病理生理学的潜在因素。然而，缺乏确切的信息之间的串扰内分泌和免疫因素的病变，以及是否有助于参与肥大细胞与疾病的病理生理。在这项研究中，我们观察到肥大细胞数量显着增加，在子宫内膜异位症病变相比，匹配的在位内膜从相同的患者。与在位子宫内膜相比，增生性病变具有显著更高水平的干细胞因子（SCF），这是一种对肥大细胞扩增、分化和组织驻留肥大细胞存活至关重要的强效生长因子。靶向mRNA Q-PCR阵列显示，肥大性病变具有有利于肥大细胞募集和随后分化的微环境（CPA 3、VCAM 1、CCL 2、CMA 1、CCR 1和KITLG的上调）。为了检查肥大细胞在肥大病变微环境中的串扰，肥大上皮细胞（12 Z）和子宫内膜基质细胞（hESC）与肥大细胞条件培养基孵育显示促炎和趋化动力学细胞因子的产生显著增加。为了进一步了解雌激素对子宫内膜异位症肥大细胞的影响，我们在C57 BL/6小鼠中诱导子宫内膜异位症。在假手术组中，雌激素处理小鼠的腹腔液中成熟肥大细胞显著高于未处理小鼠。小鼠肥大细胞病变组织显示，与对照子宫内膜相比，雌激素处理的肥大细胞病变诱导组中肥大细胞生物学相关的几个基因（qRT-PCR）显著上调。与未处理的病变或对照子宫内膜相比，雌激素处理的小鼠的子宫内膜病变也具有显著更高密度的阿辛蓝染色的肥大细胞。总的来说，这些发现表明，肥大细胞病变提供了一个必要的肥大细胞的招聘和分化的微环境。反过来，肥大细胞可能释放促炎介质，导致慢性盆腔疼痛和子宫内膜异位症疾病进展。
Endometriosis is an estrogen dependent, chronic inflammatory disease characterized by the growth of endometrial lining outside of the uterus. Mast cells have emerged as key players in regulating not only allergic responses but also other mechanisms such as angiogenesis, fibrosis, and pain. The influence of estrogen on mast cell function has also been recognized as a potential factor driving disease pathophysiology in number of allergic and chronic inflammatory conditions. However, precise information is lacking on the cross talk between endocrine and immune factors within the endometriotic lesions and whether that contributes to the involvement of mast cells with disease pathophysiology. In this study, we observed a significant increase in mast cell numbers within endometriotic lesions compared to matched eutopic endometrium from the same patients. Compared to eutopic endometrium, endometriotic lesions had significantly higher levels of stem cell factor (SCF), a potent growth factor critical for mast cell expansion, differentiation, and survival for tissue resident mast cells. Targeted mRNA Q-PCR array revealed that the endometriotic lesions harbour microenvironment (upregulation of CPA3, VCAM1, CCL2, CMA1, CCR1, and KITLG) that is conducive to mast cells recruitment and subsequent differentiation. To examine cross-talk of mast cells within the endometriotic lesion microenvironment, endometriotic epithelial cells (12Z) and endometrial stromal cells (hESC) incubated with mast cell-conditioned media showed significantly increased production of pro-inflammatory and chemokinetic cytokines. To further understand the impact of estrogen on mast cells in endometriosis, we induced endometriosis in C57BL/6 mice. Mature mast cells were significantly higher in peritoneal fluid of estrogen-treated mice compared to untreated mice within the sham operated groups. Mouse endometriotic lesion tissue revealed several genes (qRT-PCR) relevant in mast cell biology significantly upregulated in the estrogen treated, endometriosis-induced group compared to control endometrium. The endometriotic lesions from estrogen treated mice also had significantly higher density of Alcian blue stained mast cells compared to untreated lesions or control endometrium. Collectively, these findings suggest that endometriotic lesions provide a microenvironment necessary for recruitment and differentiation of mast cells. In turn, mast cells potentially release pro-inflammatory mediators that contribute to chronic pelvic pain and endometriosis disease progression.
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DOI：
10.4049/jimmunol.0904177
发表时间：
2010-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Collington SJ;Hallgren J;Pease JE;Jones TG;Rollins BJ;Westwick J;Austen KF;Williams TJ;Gurish MF;Weller CL
通讯作者：
Weller CL
影响因子：
3.7
作者：
Jensen F;Woudwyk M;Teles A;Woidacki K;Taran F;Costa S;Malfertheiner SF;Zenclussen AC
通讯作者：
Zenclussen AC
影响因子：
14.2
作者：
Dougherty, Ryan H.;Sidhu, Sukhvinder S.;Raman, Kavita;Solon, Margaret;Solberg, Owen D.;Caughey, George H.;Woodruff, Prescott G.;Fahy, John V.
通讯作者：
Fahy, John V.
影响因子：
13.3
作者：
Menzies, F. M.;Shepherd, M. C.;Nelson, S. M.
通讯作者：
Nelson, S. M.
影响因子：
4.6
作者：
Miller JE;Monsanto SP;Ahn SH;Khalaj K;Fazleabas AT;Young SL;Lessey BA;Koti M;Tayade C
通讯作者：
Tayade C