期刊
JOURNAL OF INFLAMMATION RESEARCH
卷 16, 期 -, 页码 109-126出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/JIR.S374802Journalof
关键词
theaflavin-3; 3?-digallate; autophagy; inflammation; macrophage polarization; rheumatoid arthritis
类别
By modulating autophagy, Theaflavin-3,3'-digallate (TFDG) can alleviate inflammation and promote anti-inflammatory M2 macrophage polarization, thus protecting joints against collagen-induced arthritis.
Purpose: Previous studies have presented that theaflavin-3,3'-digallate (TFDG), one of natural flavonoids, have protective effects on collagen-induced arthritis (CIA). Besides, it was reported that TFDG could affect inflammatory signaling pathways, like NF Kappa B, JNK, and so on, to ameliorate inflammation. However, the anti-inflammatory mechanisms mentioned above are common to natural flavonoid products including TFDG. Therefore, this study aimed to further investigate the other mechanisms of TFDG against CIA.Methods: DBA/1 mice (8-10 weeks) were intravenously injected Freund's Adjuvant (100 mu L) at the base of tail and intraperitoneally injected PBS or different dosage of TFDG (1 mg/kg or 10 mg/kg). Then the paw and knee tissues were collected to assess the severity of joint destruction. In vitro experiments, bone marrow macrophages (BMMs) were exposed to TNF-alpha (10ng/mL) with or without different concentrations of TFDG (0.1 mu mol/L or 1.0 mu mol/L). Besides, the targets of TFDG were predicted with docking software and were verified through experiment.Results: TFDG treatment could reduce M1 macrophage (pro-inflammatory) and inflammatory cytokines, such as IL-1, IL- 6 and TNF-alpha, both in vitro and in vivo. At the same time, the M2 macrophage (alternatively activated) polarization was promoted by TFDG. Animal experiments showed TFDG ameliorated joint destructions. For investigating the mechanisms, the targets of TFDG were predicted by bioinformatics tools. According to predictions, we hypothesized that TFDG could act with BCL-2 to weaken the interaction between BCL-2 and Beclin1. Beclin1 plays a central role in autophagy, and we found that the autophagy level of BMMs was recovered by TFDG. Besides, 3-MA, an autophagy inhibitor, could attenuate the therapeutic effect of TFDG.Conclusion: TFDG protected against collagen-induced arthritis by attenuating the inflammation and promoting anti-inflammatory M2 macrophage polarization through controlling autophagy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据