Department of Morphology and Genetics, Universidade Federal de São Paulo, Rua Botucatu 740, Edifício Lemos Torres - 3° andar, São Paulo, SP, 04023-900, Brazil.
Biosciences Graduate Program, Institute of Biosciences, Letters and Exact Sciences, Universidade Estadual Paulista (UNESP), São José do Rio Preto, Brazil.
Inflammation. 2024 Jun;47(3):1041-1052. doi: 10.1007/s10753-023-01959-3. Epub 2024 Jan 10.
Annexin A1 (AnxA1) is a glucocorticoid-inducible protein and an important endogenous modulator of inflammation. However, its effect in the endometrial microenvironment is poorly explained. This study aimed to evaluate the role of endogenous AnxA1 in an endometritis mouse model induced by lipopolysaccharide (LPS). Female C57BL/6 wild-type (WT) and AnxA1 mice were divided into two groups: SHAM and LPS. To induce endometritis, mice received a vaginal infusion of 50 μL of LPS (1 mg/mL) dissolved in phosphate-buffered saline. After 24 h, the mice were euthanized, and blood and uteri samples were collected. The endometrium inflammatory scores were significantly increased in the LPS-treated group. AnxA1 mice from the LPS group demonstrated a significant increase in the number of degranulated mast cell levels compared to AnxA1 SHAM mice. The Western blotting analysis revealed that a lack of AnxA1 promoted the upregulation of NLRP3 and pro-IL-1β in the acute endometritis animal model compared to WT LPS animals. LPS-induced endometritis increased the number of blood peripheral leukocytes in both WT and AnxA1 mice compared with SHAM group mice (p < 0.001). AnxA1 mice also showed increased plasma levels of IL-1β (p < 0.01), IL-6, IL-10, IL-17, and TNF-α (p < 0.05) following LPS-induced endometritis. In conclusion, a lack of endogenous AnxA1 exacerbated the inflammatory response in an endometritis model via NLRP3 dysregulation, increased uterine mast cell activation, and plasma pro-inflammatory cytokine release.
annexin A1 (AnxA1) 是一种糖皮质激素诱导蛋白，也是炎症的重要内源性调节剂。然而，其在子宫内膜微环境中的作用尚不清楚。本研究旨在评估内源性 AnxA1 在脂多糖（LPS）诱导的子宫内膜炎小鼠模型中的作用。将雌性 C57BL/6 野生型（WT）和 AnxA1 小鼠分为两组：SHAM 和 LPS。为了诱导子宫内膜炎，小鼠阴道内输注 50 μL 溶解在磷酸盐缓冲盐水中的 1 mg/mL LPS。24 小时后，处死小鼠，采集血液和子宫样本。LPS 处理组的子宫内膜炎评分明显升高。与 AnxA1 SHAM 小鼠相比，LPS 组的 AnxA1 小鼠脱颗粒肥大细胞水平显著增加。Western blot 分析显示，与 WT LPS 动物相比，缺乏 AnxA1 在急性子宫内膜炎动物模型中促进 NLRP3 和 pro-IL-1β 的上调。与 SHAM 组小鼠相比，LPS 诱导的子宫内膜炎增加了 WT 和 AnxA1 小鼠外周血白细胞的数量（p < 0.001）。AnxA1 小鼠在 LPS 诱导的子宫内膜炎后还表现出血浆中 IL-1β（p < 0.01）、IL-6、IL-10、IL-17 和 TNF-α 水平升高（p < 0.05）。总之，内源性 AnxA1 的缺乏通过 NLRP3 失调、增加子宫肥大细胞活化和血浆促炎细胞因子释放，加剧了子宫内膜炎模型中的炎症反应。
