Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Gynecol Obstet Invest. 2021;86(1-2):139-148. doi: 10.1159/000513590. Epub 2021 Feb 4.
Vitamin D has potent immunoregulatory features and modulates innate and adaptive immune responses. There is a significant association between intrauterine infection-associated inflammatory responses and pregnancy complications such as abortion and preterm labor. Here, we investigated how 1,25 (OH)2 D3 could modulate inflammatory responses of endometrial cells.
This is an in vitro experimental study. Endometrial stromal cells (ESCs) and whole endometrial cells (WECs) were collected from 15 apparently normal women, and the immunomodulatory effects of 1,25 (OH)2 D3 on lipopolysaccharide (LPS)- or lipoteichoic acid (LTA)-treated ESCs and WECs were investigated. Participants/Materials, Setting, and Methods: Women with no history of abortion, infertility, endometriosis, or sign of vaginal infection were enrolled in this study. Endometrial samples were collected by gynecologists using a Pipelle pipette in the proliferative phase of the menstrual cycle. WECs and ESCs were collected and treated with either LPS or LTA. The levels of IL-6, IL-8, and TNF-α in culture supernatants were quantified using the ELISA technique. TLR2, TLR4, and MyD88 expressions were assessed by RT-qPCR. TLR4 expression at the protein level was studied by the Western blot technique.
1,25 Dihydroxycholecalciferol (1,25 (OH)2 D3) significantly reduced TNF-α production in LPS-activated ESCs and TNF-α and IL-6 production by LTA-stimulated WECs. In contrast, 1,25 (OH)2 D3 pretreatment increased the production of IL-8 by LPS- and LTA-stimulated endometrial cells. 1,25 (OH)2 D3 pretreatment markedly reduced LPS-induced TLR4 protein expression by ESCs. LPS treatment of ESCs significantly induced MyD88 gene expression. This effect was reversed when these cells were pretreated with 1,25 (OH)2 D3 before stimulation with LPS.
Because of the small size of samples, doing experiments all together on some samples was not feasible. Confirmation of the results obtained here needs well-designed in vivo studies.
1,25 (OH)2 D3 is an immunomodulatory molecule essential for maintaining endometrial immune homeostasis by controlling potentially harmful inflammatory responses associated with female reproductive tract infections.
维生素 D 具有强大的免疫调节功能，并调节先天和适应性免疫反应。宫内感染相关炎症反应与流产和早产等妊娠并发症之间存在显著关联。在这里，我们研究了 1,25（OH）2 D3 如何调节子宫内膜细胞的炎症反应。
这是一项体外实验研究。从 15 名明显正常的女性中收集子宫内膜基质细胞（ESCs）和整个子宫内膜细胞（WECs），并研究 1,25（OH）2 D3 对脂多糖（LPS）或脂磷壁酸（LTA）处理的 ESCs 和 WECs 的免疫调节作用。
参与者/材料、设置和方法：招募无流产、不孕、子宫内膜异位症或阴道感染迹象的女性参加本研究。妇科医生使用 Pipelle 吸头在月经周期的增殖期采集子宫内膜样本。收集 WECs 和 ESCs 并用 LPS 或 LTA 处理。使用 ELISA 技术定量测定培养上清液中 IL-6、IL-8 和 TNF-α 的水平。通过 RT-qPCR 评估 TLR2、TLR4 和 MyD88 的表达。通过 Western blot 技术研究 TLR4 蛋白水平的表达。
1,25 二羟胆钙化醇（1,25（OH）2 D3）显著降低 LPS 激活的 ESCs 中 TNF-α的产生，以及 LTA 刺激的 WECs 中 TNF-α和 IL-6 的产生。相反，1,25（OH）2 D3 预处理增加了 LPS 和 LTA 刺激的子宫内膜细胞中 IL-8 的产生。1,25（OH）2 D3 预处理显著降低了 LPS 诱导的 ESCs 中 TLR4 蛋白表达。LPS 处理 ESCs 显著诱导了 MyD88 基因表达。当这些细胞在用 LPS 刺激之前用 1,25（OH）2 D3 预处理时，这种作用被逆转。
由于样本量小，在一些样本上一起进行实验是不可行的。需要设计良好的体内研究来证实这里获得的结果。
1,25（OH）2 D3 是一种免疫调节分子，通过控制与女性生殖道感染相关的潜在有害炎症反应，对维持子宫内膜免疫稳态至关重要。
