Epigenetic Regulation of Interleukin-17-Related Genes and Their Potential Roles in Neutrophil Vascular Infiltration in Preeclampsia.
Epigenetic Regulation of Interleukin-17-Related Genes and Their Potential Roles in Neutrophil Vascular Infiltration in Preeclampsia.
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白细胞介素17相关基因的表观遗传调控及其在子痫前期神经血管浸润中的潜在作用
DOI：
10.1007/s43032-021-00605-3
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Strauss JF 3rd
中科院分区：
文献类型：
--
作者：
Walsh SW;Nugent WH;Archer KJ;Al Dulaimi M;Washington SL;Strauss JF 3rd
DNA甲基化是一种控制基因表达的表观遗传机制，甲基化降低与基因表达增加相关。我们假设IL-17细胞因子受DNA甲基化调节，在子痫前期妇女的循环中升高，并刺激血管中性粒细胞趋化因子的表达，这可能解释了子痫前期中性粒细胞的血管浸润。我们发现，子痫前期女性大网膜动脉中IL17A、IL17E和IL17F基因的DNA甲基化显著降低，调节IL-17生成t淋巴细胞的il - 2基因甲基化显著降低，与淋巴细胞功能相关的中性粒细胞趋化因子和TNFα受体编码基因甲基化显著降低。与正常妊娠相比，子痫前期妊娠中期孕妇血浆IL-17A水平显著升高。为了测试甲基化是否调节IL-17细胞因子，用低甲基化剂培养淋巴细胞系（Jurkat）。低甲基化增加了IL17E（又称IL25）、IL17F和IL2的表达。Jurkat细胞不表达IL17A。为了检测IL-17细胞因子在子痫前期血管中性粒细胞浸润中的潜在作用，我们用IL-17细胞因子培养人血管平滑肌细胞。IL-17A增加了子痫前期妇女血管平滑肌中增高的中性粒细胞趋化因子（IL-8、CXCL5和CXCL6）的基因表达，而IL-17E和IL-17F则没有。单核细胞趋化因子CCL-2未升高。TNFα也增加中性粒细胞趋化因子。IL-17细胞因子受DNA甲基化调控，IL-17A在子痫前期升高并刺激血管平滑肌中性粒细胞趋化因子的表达。IL-17A可能与子痫前期中性粒细胞的血管浸润有关。
DNA methylation is an epigenetic mechanism controlling gene expression, and reduced methylation is associated with increased gene expression. We hypothesized that IL-17 cytokines are regulated by DNA methylation, are elevated in the circulation of preeclamptic women, and stimulate vascular neutrophil chemokine expression, which could account for vascular infiltration of neutrophils in preeclampsia. We found significantly reduced DNA methylation of IL17A, IL17E and IL17F genes in omental arteries of preeclamptic women, significantly reduced methylation of IL2, which regulates IL-17- producing T-lymphocytes, and significantly reduced methylation of genes encoding neutrophil chemokines and TNFα receptors related to lymphocyte function. Maternal plasma levels of IL-17A were significantly elevated in the second trimester of preeclamptic pregnancy as compared to normal pregnancy. To test if methylation regulates IL-17 cytokines, a lymphocyte cell line (Jurkat) was cultured with a hypomethylating agent. Hypomethylation increased expression of IL17E (aka IL25), IL17F and IL2. IL17A was not expressed by Jurkat cells. To test the potential role of IL-17 cytokines in vascular neutrophil infiltration associated with preeclampsia, human vascular smooth muscle cells were cultured with IL-17 cytokines. IL-17A, but not IL-17E or IL-17F, increased gene expression of neutrophil chemokines (IL-8, CXCL5 and CXCL6) that are increased in vascular smooth muscle of preeclamptic women. The monocyte chemokine, CCL-2, was not increased. TNFα also increased neutrophil chemokines. IL-17 cytokines are regulated by DNA methylation, IL-17A is elevated in preeclampsia and stimulates expression of neutrophil chemokines in vascular smooth muscle. IL-17A could be responsible for vascular infiltration of neutrophils in preeclampsia.
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影响因子：
7.2
作者：
Kupferminc, MJ;Peaceman, AM;Socol, ML
通讯作者：
Socol, ML
影响因子：
9.8
作者：
Sibai, Baha;Romero, Roberto;Klebanoff, Mark A.;Rice, Madeline Murguia;Caritis, Steve;Lindheimer, Marshall D.;Van Dorsten, J. Peter;Landon, Mark;Miodovnik, Menachem;Dombrowski, Mitchell;Meis, Paul
通讯作者：
Meis, Paul
DOI：
10.1161/hypertensionaha.111.176602
发表时间：
2011-11
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Mishra N;Nugent WH;Mahavadi S;Walsh SW
通讯作者：
Walsh SW
影响因子：
2.1
作者：
Lurie, S;Frenkel, E;Tuvbin, Y
通讯作者：
Tuvbin, Y
影响因子：
9.8
作者：
Hayashi, M;Hamada, Y;Ohkura, T
通讯作者：
Ohkura, T