Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic.
Laboratory of Genome Integrity, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
Ann Anat. 2021 Jul;236:151671. doi: 10.1016/j.aanat.2020.151671. Epub 2021 Jan 10.
The success of pregnancy depends on the regulation of immunological processes in the placenta. Important mediators of an immune response include pro- and anti-inflammatory interleukins which may be regulated by CYP epoxygenases and their metabolites. The relation between interleukins and CYP epoxygenases expression in human placenta has not yet been studied vastly.
We investigated the expression patterns of IL-1β and IL-10 in embryonic (n=8), early foetal (n=16) and term (n=7) human placenta tissue by an immunohistochemical method and evaluated the results by Kruskal-Wallis test. The obtained data was correlated using Spearman's correlation coefficient to our previously published data of CYP epoxygenases expression in the same samples. To confirm that Hofbauer cells express IL-10 and IL-1β as well as CYP2C8 and IL-10 together, and thus there is a relation between proteins of interests, we used multiplex immunofluorescent staining.
The expression of IL-1β decreased with gestational age in cytotrophoblast, syncytiotrophoblast, as well as in Hofbauer cells whilst IL-10 decreased in cytotrophoblast, remained at the same levels in syncytiotrophoblast and increased in Hofbauer cells. In trophoblast cells, we found a statistically significant positive correlation between the expression of CYP2J2 and CYP2C9 with IL-1β, whereas there was no relation between IL-10 and any of the tested CYP epoxygenases. In Hofbauer cells, we found a significant positive correlation between CYP2C8 and IL-10 and a significant negative correlation between CYP2C8 and IL-1β.
Our results showed that the exact role and relation of interleukins and CYP epoxygenases and their metabolites is dependent on their respective cellular context. Because of IL-10, IL-1β, as well as HBCs play a role in various pathological conditions, further investigation of the exact role of CYP epoxygenase, interleukins and their relations is needed.
妊娠的成功取决于胎盘内免疫过程的调节。免疫反应的重要介质包括促炎和抗炎细胞因子，它们可能受 CYP 环氧合酶及其代谢物的调节。细胞因子与人类胎盘 CYP 环氧合酶表达之间的关系尚未得到广泛研究。
我们通过免疫组织化学方法研究了 IL-1β 和 IL-10 在胚胎（n=8）、早期胎儿（n=16）和足月（n=7）人胎盘组织中的表达模式，并通过 Kruskal-Wallis 检验评估了结果。使用 Spearman 相关系数将获得的数据与我们之前在相同样本中发表的 CYP 环氧合酶表达数据相关联。为了证实 Hofbauer 细胞表达 IL-10 和 IL-1β 以及 CYP2C8 和 IL-10 一起，并且蛋白之间存在关系，我们使用了多重免疫荧光染色。
在滋养细胞、合体滋养细胞和 Hofbauer 细胞中，IL-1β 的表达随着胎龄的增加而减少，而 IL-10 的表达在滋养细胞中减少，在合体滋养细胞中保持不变，在 Hofbauer 细胞中增加。在滋养细胞中，我们发现 CYP2J2 和 CYP2C9 与 IL-1β 的表达呈统计学显著正相关，而 IL-10 与任何测试的 CYP 环氧合酶均无关系。在 Hofbauer 细胞中，我们发现 CYP2C8 与 IL-10 呈显著正相关，与 IL-1β 呈显著负相关。
我们的结果表明，细胞因子和 CYP 环氧合酶及其代谢物的确切作用和关系取决于它们各自的细胞环境。由于 IL-10、IL-1β 和 Hofbauer 细胞在各种病理条件下发挥作用，需要进一步研究 CYP 环氧合酶、细胞因子及其关系的确切作用。
