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炎性细胞因子对小鼠子宫收缩的直接影响。

Direct Effects of Inflammatory Cytokines on Mouse Uterine Contraction.

机构信息

Guangzhou Key Laboratory of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Department of Blood Transfusion, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

出版信息

Am J Reprod Immunol. 2024 Oct;92(4):e13938. doi: 10.1111/aji.13938.

DOI:10.1111/aji.13938
PMID:39403002
Abstract

PROBLEM

Uterine contractions signal labor onset, with elevated pro-inflammatory cytokines playing a pivotal role. Prior studies have explored their effects on prostaglandins, oxytocin, and signaling pathways, but have overlooked their direct effects on uterine contractions. Here, we aim to investigate the direct effects of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) on contractions to ascertain if they have immediate observable effects like those reported for lipopolysaccharide (LPS) and other effects.

METHOD OF STUDY

Tension recordings were used to assess the direct effects of cytokines and/or LPS on mouse uterine contractions. Calcium imaging was employed to observe calcium oscillations in cytokine-pretreated myometrial smooth muscle cells (MSMCs) in response to oxytocin. The release of inflammatory cytokines and chemokines from uterine explants after LPS and/or cytokines application was investigated using Luminex.

RESULTS

IL-1β, IL-6, and TNF-α rapidly enhanced contractions of term pregnant mouse uterus. LPS combined with TNF-α intensified contractions compared to LPS alone, although this effect was not statistically significant in our results (p > 0.050). Pretreatment of MSMCs with IL-1β, IL-6, or TNF-α increased calcium oscillations in response to oxytocin. LPS and/or cytokine significantly stimulated the release of IL-1β, IL-6, TNF-α, Chemokine (C-X-C motif) ligand 1 (CXCL1), and monocyte chemoattractant protein-1 (MCP1) from uterine explants in vitro.

CONCLUSIONS

Inflammatory cytokines have short-term and long-term effects on mouse uterine contractions, which together contribute to progressively stronger contractions during labor.

摘要

问题

子宫收缩标志着分娩开始,升高的促炎细胞因子起着关键作用。先前的研究已经探讨了它们对前列腺素、催产素和信号通路的影响,但忽略了它们对子宫收缩的直接影响。在这里,我们旨在研究白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)对收缩的直接影响,以确定它们是否具有与脂多糖(LPS)和其他作用类似的直接可观察作用。

研究方法

张力记录用于评估细胞因子和/或 LPS 对小鼠子宫收缩的直接影响。钙成像用于观察细胞因子预处理的子宫平滑肌细胞(MSMC)对催产素的钙振荡。使用 Luminex 研究 LPS 和/或细胞因子应用后子宫外植体中促炎细胞因子和趋化因子的释放。

结果

IL-1β、IL-6 和 TNF-α 可迅速增强足月妊娠小鼠子宫的收缩。与单独 LPS 相比,LPS 与 TNF-α 联合使用可增强收缩,但我们的结果在统计学上无显著差异(p > 0.050)。IL-1β、IL-6 或 TNF-α 预处理 MSMC 可增加对催产素的钙振荡。LPS 和/或细胞因子显著刺激子宫外植体中白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α、趋化因子(C-X-C 基序)配体 1(CXCL1)和单核细胞趋化蛋白-1(MCP1)的释放。

结论

炎症细胞因子对小鼠子宫收缩具有短期和长期影响,共同导致分娩过程中子宫收缩逐渐增强。

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