抗微生物CATH-2减弱了禽类致病性E. 通过NF-κB/NLRP3/MAPK途径诱导的炎症反应和巨细胞中的溶酶体功能障碍
Yating Xu1, Liuyi Xu1, Tingting Zhang1
1Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing 400715, China.
International journal of molecular sciences
|December 17, 2024
概括
肉甲基西丁-2 (CATH-2) 通过破坏 lysosomal 功能和抑制 NF-κB/NLRP3/MAPK 途径在禽病原性大肠杆菌感染期间减少炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 微生物学 微生物学
背景情况:
- 凯瑟利西丁具有抗炎性质.
- 肉的cathelicidin-2 (CATH-2) 调节免疫反应,但其抗炎机制尚不清楚.
- 禽类致病性大肠杆菌 (APEC) 感染会在宿主细胞中引发炎症反应.
研究的目的:
- 在APEC感染期间研究CATH-2在小鼠腹巨细胞上的抗炎活性.
- 阐明CATH-2抗炎作用的潜在分子机制.
- 确定 lysosomal 功能和特定信号通路在 CATH-2 的作用中的作用.
主要方法:
- 小鼠腹巨细胞被CATH-2原始化,随后被APEC感染.
- 测量了细胞因子的产生 (IL-1β,IL-6,IL-1α,IL-12).
- 评估了卡斯巴酶-1激活,NLRP3炎症酶组合,NF-κB和MAPK信号通路.
- 评估了 Lysosomal 功能,包括 cathepsin B 表达和酸化.
- 研究了ML-SA1对溶酶体酸化和CATH-2抗炎活性的影响.
主要成果:
- 在CATH-2原始化中,可显著降低促炎性细胞因子 (IL-1β,IL-6,IL-1α,IL-12) 的产生.
- 在CATH-2减弱的APEC诱导的酶-1激活和NLRP3炎症酶组合.
- CATH-2抑制了NF-κB和MAPK信号通路的激活.
- CATH-2通过抑制甲素B mRNA表达和 lysosomal 酸化来破坏 lysosomal 功能.
- 使用ML-SA1增强 lysosomal 酸化,降低了CATH-2的抗炎作用.
结论:
- 在巨细胞中,CATH-2对APEC感染具有显著的抗炎活性.
- 通过向NF-κB/NLRP3/MAPK通路,CATH-2可以抑制炎症.
- 在部分情况下,CATH-2通过破坏 lysosomal 功能来发挥其抗炎作用.
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