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Resistin, an adipokine with potent proinflammatory properties 总被引:33,自引:0,他引:33
Bokarewa M Nagaev I Dahlberg L Smith U Tarkowski A 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(9):5789-5795
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Biao Wang Xueyi Li Ming Li Yan Geng Na Wang Yaofeng Jin Wen Zhang Ke Xu Jing Wang Li Tao Simin Lai Kunyi Wu Jing Lei Jing Wang Ting Zhou Ke Li Yanjiong Chen Li Xue 《Cell death & disease》2022,13(3)
Dopamine receptors are involved in several immunological diseases. We previously found that dopamine D3 receptor (D3R) on mast cells showed a high correlation with disease activity in patients with rheumatoid arthritis, but the mechanism remains largely elusive. In this study, a murine collagen-induced arthritis (CIA) model was employed in both DBA/1 mice and D3R knockout mice. Here, we revealed that D3R-deficient mice developed more severe arthritis than wild-type mice. D3R suppressed mast cell activation in vivo and in vitro via a Toll-like receptor 4 (TLR4)-dependent pathway. Importantly, D3R promoted LC3 conversion to accelerate ubiquitin-labeled TLR4 degradation. Mechanistically, D3R inhibited mTOR and AKT phosphorylation while enhancing AMPK phosphorylation in activated mast cells, which was followed by autophagy-dependent protein degradation of TLR4. In total, we found that D3R on mast cells alleviated inflammation in mouse rheumatoid arthritis through the mTOR/AKT/AMPK-LC3-ubiquitin-TLR4 signaling axis. These findings identify a protective function of D3R against excessive inflammation in mast cells, expanding significant insight into the pathogenesis of rheumatoid arthritis and providing a possible target for future treatment.Subject terms: Immunological disorders, Rheumatic diseases 相似文献
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