College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, PR China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, PR China.
PLoS One. 2022 Apr 27;17(4):e0266144. doi: 10.1371/journal.pone.0266144. eCollection 2022.
Postpartum uterine infection in dairy cows is commonly caused by pathogenic bacteria such as Escherichia coli (E. coli). Progesterone elicits immunosuppressive function within bovine endometrium, and has been suggested to be related to postpartum uterine infection. Endometrial stroma is exposed to bacteria due to the disruption of epithelium during parturition, but the effect and mechanism of progesterone on innate immune response of stromal cells has not been reported. This study evaluated the impact of progesterone on inflammatory response of primary endometrial stromal cells stimulated by lipopolysaccharide or heat-killed E. coli. Quantitative PCR analysis revealed that progesterone repressed mRNA induction of IL1B, IL6, TNF, CXCL8, NOS2, and PTGS2 in stromal cells in response to lipopolysaccharide or E. coli challenge. Consistently, Western blot and immunofluorescence staining results showed that progesterone suppressed lipopolysaccharide- or E. coli-induced MAPK and NF-κB activations characterized with decreased phosphorylations of ERK1/2, JNK, P38, IκBα, and P65, and inhibition of P65 nuclear translocation. In unstimulated stromal cells, progesterone alone did not affect the mRNA transcription for IL6, TNF, CXCL8, NOS2, and PTGS2, and the signaling cascade of MAPK and NF-κB, but decreased IL1B mRNA expression. These results revealed that the anti-inflammatory effect of progesterone in lipopolysaccharide- or E. coli-challenged endometrial stromal cells was probably mediated through MAPK and NF-κB pathways.
奶牛产后子宫感染通常是由大肠杆菌（E. coli）等病原菌引起的。孕激素在牛子宫内膜中引发免疫抑制功能，并且与产后子宫感染有关。由于分娩过程中上皮细胞的破坏，子宫内膜基质暴露于细菌，但孕激素对基质细胞固有免疫反应的影响和机制尚未报道。本研究评估了孕激素对脂多糖或热灭活大肠杆菌刺激的原代子宫内膜基质细胞炎症反应的影响。定量 PCR 分析显示，孕激素抑制了基质细胞对脂多糖或大肠杆菌刺激的 IL1B、IL6、TNF、CXCL8、NOS2 和 PTGS2 的 mRNA 诱导。Western blot 和免疫荧光染色结果一致表明，孕激素抑制了脂多糖或大肠杆菌诱导的 MAPK 和 NF-κB 激活，表现为 ERK1/2、JNK、P38、IκBα 和 P65 的磷酸化减少，以及 P65 核易位的抑制。在未受刺激的基质细胞中，孕激素单独作用不会影响 IL6、TNF、CXCL8、NOS2 和 PTGS2 的 mRNA 转录以及 MAPK 和 NF-κB 的信号级联，但会降低 IL1B 的 mRNA 表达。这些结果表明，孕激素在脂多糖或大肠杆菌刺激的子宫内膜基质细胞中的抗炎作用可能是通过 MAPK 和 NF-κB 途径介导的。
