Myeloid Vamp3 deletion attenuates CFA-induced inflammation and pain in mice via ameliorating macrophage infiltration and inflammatory cytokine production

Frontiers in Immunology

Immunology

Yang Liu¹  Xiaolong Dai¹  Ruizhen Wang¹  Qianqian Fan¹  Xinrong Yan¹  Wenhao Zhang¹  Lianlian Li¹  Weiwei Chen¹  Jiafu Wang²  Jianghui Meng² 

[1] School of Life Sciences, Henan University, Kaifeng, China;School of Life Sciences, Henan University, Kaifeng, China;School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin, Ireland;

关键词: vesicle associated membrane protein;    inflammation;    cytokine;    rheumatoid arthritis;    pain;    SNARE;    therapeutics;    neuropeptides;   

DOI  :  10.3389/fimmu.2023.1239592

 received in 2023-06-13, accepted in 2023-10-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

Persistent inflammation and associated pain significantly impact individuals’ quality of life, posing substantial healthcare challenges. Proinflammatory cytokines, released by activated macrophages, play crucial roles in the development of chronic inflammatory conditions such as rheumatoid arthritis. To identify and evaluate potential therapeutic interventions targeting this process for mitigating inflammation and pain, we created myeloid cell-specific knockout of Vamp3 (vesicle-associated membrane protein 3) mice (Vamp3Δmyel) by crossing LysM-Cre mice with newly engineered Vamp3flox/flox mice. Bone marrow-derived macrophages and peritoneal resident macrophages from Vamp3Δmyel mice exhibited a significant reduction in TNF-α and IL-6 release compared to control mice. Moreover, Vamp3 deficiency led to decreased paw edema and ankle joint swelling induced by intraplantar injection of complete Freund’s adjuvant (CFA). Furthermore, Vamp3 depletion also mitigated CFA-induced mechanical allodynia and thermal hyperalgesia. Mechanistically, Vamp3 loss ameliorated the infiltration of macrophages in peripheral sites of the hind paw and resulted in reduced levels of TNF-α and IL-6 in the CFA-injected paw and serum. RT-qPCR analysis demonstrated downregulation of various inflammation-associated genes, including TNF-α, IL-6, IL-1β, CXCL11, TIMP-1, COX-2, CD68, and CD54 in the injected paw at the test day 14 following CFA administration. These findings highlight the novel role of Vamp3 in regulating inflammatory responses and suggest it as a potential therapeutic target for the development of novel Vamp-inactivating therapeutics, with potential applications in the management of inflammatory diseases.

【 授权许可】

Unknown   
Copyright © 2023 Dai, Li, Yan, Fan, Wang, Zhang, Chen, Liu, Meng and Wang