阻断CCL5/CCL7-CCR1轴通过NF-κB通路调节巨细胞极化,以缓解骨关节炎的进展
Hanqing Xu1, Yi He2, Sheng Chen1
1Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan City, Hubei Province, China.
International immunopharmacology
|January 13, 2025
概括
通过阻断CCL5/CCL7-CCR1轴,可以减少M1巨细胞的两极分化,通过抑制NF-κB通路来缓解骨关节炎的进展和肌炎.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 细胞生物学 细胞生物学
背景情况:
- 骨关节炎 (OA) 是一种退行性关节疾病,其特征是软骨分解.
- 巨细胞两极分化在OA的发病过程中起着至关重要的作用.
- 化基因受体CCR1及其连接体与炎症过程有关.
研究的目的:
- 为了研究CCR1轴在巨细胞极化中的作用.
- 评估CCR1抑制在骨关节炎中的治疗潜力.
主要方法:
- RAW巨细胞被两极分化为M1/M2亚型,并用CCR1抑制剂BX471.1进行治疗.
- 使用RT-qPCR,免疫光和流细胞计,评估了巨细胞的两极化.
- 在体内研究中使用了DMM小鼠模型,用BX471.1治疗.
主要成果:
- 抑制CCR1及其配体 (CCL5,CCL7) 的沉默降低了M1巨细胞的极化.
- CCR1阻塞减少了NF-κB通路的激活和随后的软骨损伤.
- 在体内,CCR1抑制减少了M1巨细胞的透,并缓解了关节软骨损伤.
结论:
- CCL5/CCL7-CCR1轴是OA中巨分化的一个关键调节器.
- 针对这一轴提供了一种潜在的治疗策略,以减少突炎和减缓OA的进展.
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