Department of Endocrinology, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China.
Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
J Clin Endocrinol Metab. 2024 Jan 18;109(2):333-343. doi: 10.1210/clinem/dgad531.
Placenta-derived inflammation plays a vital role in the pathophysiology of gestational diabetes mellitus (GDM). IL-32 is a novel pro-inflammatory cytokine and metabolic regulator involved in the development of metabolic disease. We investigated the effect of IL-32 in GDM.
First-trimester C-reactive protein (CRP) level was monitored in a case-control study of 186 women with GDM and 186 women without. Placental tissue was lysed and analyzed by high-resolution liquid chromatography-tandem mass spectrometry. Circulating level of inflammatory cytokines IL-32, IL-6, and TNF-α were measured by ELISA kits. The expression of placenta-derived macrophages, inflammatory cytokines, and related pathway proteins were assessed by reverse transcriptase-quantitative PCR, western blot, immunohistochemistry, or immunofluorescence.
First-trimester CRP level in peripheral blood was closely associated with glucose and insulin resistance index and was an independent correlation with the development of GDM. High-resolution liquid chromatography-tandem mass spectrometry revealed that placenta-derived CRP expression was dramatically elevated in women with GDM. Interestingly, the expression of placenta-derived IL-32 was also increased and located in the macrophages of placental tissue. Meanwhile, the expression of IL-6, TNF-α, and p-p38 were up-regulated in the placental tissues with GDM. Either IL-6 or TNF-α was colocated with IL-32 in the placental tissue. Importantly, circulating IL-32 throughout pregnancy was increased in GDM and was related to placental-derived IL-32 expression, circulating IL-6, and TNF-α, glucose and insulin resistance index.
Increased circulating IL-32 throughout pregnancy was closely associated with placenta macrophage-derived IL-32 expression and GDM. First trimester IL-32 level in peripheral blood may serve to predict the development of GDM.
胎盘来源的炎症在妊娠期糖尿病（GDM）的病理生理学中起着至关重要的作用。IL-32 是一种新型的促炎细胞因子和代谢调节剂，参与代谢疾病的发生。我们研究了 IL-32 在 GDM 中的作用。
在一项 186 例 GDM 妇女和 186 例非 GDM 妇女的病例对照研究中，监测了她们的孕早期 C 反应蛋白（CRP）水平。通过高分辨率液相色谱-串联质谱法对胎盘组织进行裂解和分析。通过 ELISA 试剂盒测量循环中炎症细胞因子 IL-32、IL-6 和 TNF-α 的水平。通过逆转录定量 PCR、western blot、免疫组织化学或免疫荧光法评估胎盘来源的巨噬细胞、炎症细胞因子和相关通路蛋白的表达。
外周血中孕早期 CRP 水平与血糖和胰岛素抵抗指数密切相关，是 GDM 发生的独立相关因素。高分辨率液相色谱-串联质谱法显示，GDM 妇女胎盘来源的 CRP 表达显著升高。有趣的是，胎盘来源的 IL-32 表达也增加，位于胎盘组织的巨噬细胞中。同时，GDM 胎盘组织中 IL-6、TNF-α 和 p-p38 的表达上调。重要的是，IL-32 在整个孕期循环中增加，与胎盘来源的 IL-32 表达、循环中 IL-6 和 TNF-α、血糖和胰岛素抵抗指数有关。
整个孕期循环中 IL-32 的增加与胎盘巨噬细胞来源的 IL-32 表达和 GDM 密切相关。孕早期外周血中 IL-32 水平可能有助于预测 GDM 的发生。
