Beijing Key Laboratory of Dairy Cow Nutrition, Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
Beijing Key Laboratory of Dairy Cow Nutrition, Key Laboratory of Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
Int Immunopharmacol. 2022 Nov;112:109206. doi: 10.1016/j.intimp.2022.109206. Epub 2022 Sep 1.
Streptococcus agalactiae is one of the main pathogens associated with bovine mastitis. The invasion of S. agalactiae in bovine mammary epithelial cells (BMECs) has been implicated as a key event in the pathogenesis of mastitis. Matrine is known for its various pharmacological activities, such as immune response regulation and anti-inflammation. The primary aim of the research was to investigate the preventive effect of matrine on S. agalactiae-induced inflammation in BMECs along with underlying molecular mechanisms. Our data showed matrine at the concentrations of 50-100 μg/mL promoted BMECs proliferation without infection, and decreased cytotoxicity induced by S. agalactiae. Subsequently, BMECs were pre-treated with matrine (50, 75, or 100 μg/mL) for 24 h, followed by the infection with S. agalactiae for an additional 6 h. Pretreatment with matrine followed by S. agalactiae treatment decreased cell apoptosis of BMECs. Also, pretreatment of matrine to BMECs prevented the invasion of S. agalactiae. The mRNA abundances of IL-1β, IL-6, IL-8, and TNF-α were down-regulated in S. agalactiae-infected cells pretreated with matrine. In addition, the greater ratios of protein NF-κB p-p65/p65, p-IκBα/IκBα, p-38/38, and p-ERK/ERK induced by S. agalactiae were attenuated due to matrine treatment. Furthermore, pretreatment of BMECs with matrine impeded the degradation of TAK1 induced by S. agalactiae infection. These results suggest matrine could be a potential modulator in immune response of the mammary gland. In conclusion, matrine prevents cellular damage due to S. agalactiae infection by the modulation of NF-κB and MAPK signaling pathways and pro-inflammatory cytokine production.
无乳链球菌是引起奶牛乳腺炎的主要病原体之一。无乳链球菌侵入奶牛乳腺上皮细胞（BMECs）被认为是乳腺炎发病机制中的关键事件。苦参碱以其多种药理活性而闻名，如免疫反应调节和抗炎作用。本研究的主要目的是研究苦参碱对无乳链球菌诱导的 BMECs 炎症的预防作用及其潜在的分子机制。我们的数据显示，苦参碱在 50-100μg/mL 的浓度下促进 BMECs 增殖而不被感染，并降低无乳链球菌引起的细胞毒性。随后，用苦参碱（50、75 或 100μg/mL）预处理 BMECs 24 小时，然后用无乳链球菌感染 6 小时。苦参碱预处理后再用无乳链球菌处理可减少 BMECs 的细胞凋亡。此外，苦参碱预处理可阻止无乳链球菌的入侵。苦参碱预处理可下调无乳链球菌感染细胞中 IL-1β、IL-6、IL-8 和 TNF-α 的 mRNA 丰度。此外，由于苦参碱的处理，无乳链球菌诱导的 NF-κB p-p65/p65、p-IκBα/IκBα、p-38/38 和 p-ERK/ERK 蛋白的比值增加。此外，苦参碱预处理可阻止无乳链球菌感染引起的 TAK1 降解。这些结果表明，苦参碱可能是一种潜在的乳腺免疫反应调节剂。总之，苦参碱通过调节 NF-κB 和 MAPK 信号通路和促炎细胞因子的产生来防止因无乳链球菌感染引起的细胞损伤。
