Cheng Yuli, Yu Yan, Zhuang Qinghui, Wang Lei, Zhan Bin, Du Suqin, Liu Yiqi, Huang Jingjing, Hao Junfeng, Zhu Xinping
Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China.
Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, PR China.
iScience. 2022 Feb 24;25(3):103979. doi: 10.1016/j.isci.2022.103979. eCollection 2022 Mar 18.
Helminths and helminth-derived products hold promise for treating joint bone erosion in rheumatoid arthritis (RA). However, the mechanisms of helminths ameliorating the osteoclastic bone destruction are incompletely understood. Here, we report that infection or treatment with the excreted/secreted products of muscle larvae (MES) attenuated bone erosion and osteoclastogenesis in mice with collage-induced arthritis (CIA) through inhibiting M1 monocyte/macrophage polarization and the production of M1-related proinflammatory cytokines. , MES inhibited LPS-induced M1 macrophage activation while promoting IL-4-induced M2 macrophage polarization. Same effects of MES were also observed in monocytes derived from RA patients, wherein MES treatment suppressed LPS-induced M1 cytokine production. Moreover, MES treatment attenuated LPS and RANKL co-stimulated osteoclast differentiation from the RAW264.7 macrophages through inhibiting activation of the NF-κB rather than MAPK pathway. This study provides insight into the M1 subset as a potential target for helminths to alleviate osteoclastic bone destruction in RA.
蠕虫及其衍生产品有望用于治疗类风湿性关节炎(RA)中的关节骨侵蚀。然而,蠕虫改善破骨细胞性骨破坏的机制尚未完全明确。在此,我们报告,用肌肉幼虫的排泄/分泌产物(MES)感染或处理胶原诱导性关节炎(CIA)小鼠,可通过抑制M1单核细胞/巨噬细胞极化以及M1相关促炎细胞因子的产生,减轻骨侵蚀和破骨细胞生成。MES抑制脂多糖(LPS)诱导的M1巨噬细胞活化,同时促进白细胞介素-4(IL-4)诱导的M2巨噬细胞极化。在类风湿性关节炎患者来源的单核细胞中也观察到MES的相同作用,其中MES处理可抑制LPS诱导的M1细胞因子产生。此外,MES处理通过抑制核因子-κB(NF-κB)而非丝裂原活化蛋白激酶(MAPK)途径的激活,减弱LPS和核因子-κB受体活化因子配体(RANKL)共同刺激RAW264.7巨噬细胞的破骨细胞分化。本研究深入探讨了M1亚群作为蠕虫减轻类风湿性关节炎中破骨细胞性骨破坏的潜在靶点。