Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Front Immunol. 2018 Aug 22;9:1916. doi: 10.3389/fimmu.2018.01916. eCollection 2018.
Bovine endometritis affects milk production and reproductive performance in dairy cows and causes serious economic loss. The underlying molecular mechanisms or signaling pathways of bovine endometritis remain unclear. In this study, we attempted to determine the expression mechanism of mir-223 in endometritis of dairy cows and evaluate its potential therapeutic value. We first confirmed that there was an increased level of miR-223 in endometritis, and then, an LPS-induced bovine endometrial epithelial cell (BEND) line was used to mimic the inflammatory model . Our data showed that activation of NF-κB promoted the transcription of miR-223, thus inhibiting activation of the inflammatory mediator NLRP3 and its mediation of IL-1β production to protect against inflammatory damage. Meanwhile, studies showed that inhibition of mir-223 resulted in an enhanced pathology of mice during LPS-induced endometritis, while overexpression of mir-223 attenuated the inflammatory conditions in the uterus. In summary, our study highlights that miR-223 serves both to constrain the level of NLRP3 activation and to act as a protective factor in the inflammatory response and thus provides a future novel therapeutic modality for active flares in cow endometritis and other inflammatory diseases.
奶牛子宫内膜炎影响奶牛的产奶量和繁殖性能，并造成严重的经济损失。奶牛子宫内膜炎的潜在分子机制或信号通路尚不清楚。在这项研究中，我们试图确定 mir-223 在奶牛子宫内膜炎中的表达机制，并评估其潜在的治疗价值。我们首先证实 miR-223 在子宫内膜炎中水平升高，然后使用 LPS 诱导的牛子宫内膜上皮细胞（BEND）系模拟炎症模型。我们的数据表明，NF-κB 的激活促进了 miR-223 的转录，从而抑制了炎症介质 NLRP3 的激活及其介导的 IL-1β 的产生，以防止炎症损伤。同时，研究表明，抑制 mir-223 会导致 LPS 诱导的子宫内膜炎中小鼠的病理加重，而过表达 mir-223 则减轻了子宫的炎症状态。总之，我们的研究强调，miR-223 既可以限制 NLRP3 激活的水平，又可以作为炎症反应中的保护因子，因此为奶牛子宫内膜炎和其他炎症性疾病的活动发作提供了一种新的治疗方法。
