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Stefin B alleviates the gouty arthritis in mice by inducing the M2 polarization of macrophages.

ABSTRACT: The present study aims to explore the therapeutic effect of Stefin B on gouty arthritis (GA) and the polarization of macrophages in mice. Stefin B-overexpressed or knockdown M0 macrophages were constructed. The GA model was established in mice by injecting 25 mg/mL MSU, followed by a single injecting of Stefin B-overexpressing adenovirus vector (GA model + Stefin B OE) or an empty vector (GA model + Stefin B OE NC). Stefin B was found lowly expressed in M1 macrophages. CD206 was markedly upregulated and IL-10 release was signally increased in Stefin B-overexpressed macrophages. In gouty arthritis mice, marked redness and swelling were observed in the ankle joint. Dramatical infiltration of inflammatory cells was observed in the GA model and GA model + Stefin B OE NC groups, which was suppressed in the Stefin B OE group. Increased proportion of F4/80⁺CD86⁺ cells observed in GA mice was markedly repressed by Stefin B overexpression, accompanied by the declined level of Caspase-1 and IL-17. Collectively, Stefin B alleviated the GA in mice by inducing the M2 polarization of macrophages.

SUBMITTER: Lin S

PROVIDER: S-EPMC11329408 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Stefin B alleviates the gouty arthritis in mice by inducing the M2 polarization of macrophages.

Lin Shishui S Hu Xu X Li Yang Y Huang Jiyue J Zhang Rui R Bai Xinxin X Weng Shaohuang S Chen Min M

Naunyn-Schmiedeberg's archives of pharmacology 20240131 8

The present study aims to explore the therapeutic effect of Stefin B on gouty arthritis (GA) and the polarization of macrophages in mice. Stefin B-overexpressed or knockdown M0 macrophages were constructed. The GA model was established in mice by injecting 25 mg/mL MSU, followed by a single injecting of Stefin B-overexpressing adenovirus vector (GA model + Stefin B OE) or an empty vector (GA model + Stefin B OE NC). Stefin B was found lowly expressed in M1 macrophages. CD206 was markedly upregul ...[more]

PMID: 38294507

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Project description:Gouty arthritis (GA) is a form of arthritis caused by uric acid deposition in the joints that result in intense inflammation and pain. Accumulating evidence showed the importance of the sensory neurons signal upon immune cells by releasing neuropeptides and chemokines to regulate associated immune-inflammatory response. In this study, we investigated the significance of sensory neuron neuropeptides and chemokine signals on inflammation-induced macrophages polarization during GA. Methods: We screened the mRNA expression profile during GA in dorsal root ganglion (DRG) neurons to identify the most likely candidate that mediates the neuro-immune communication. Then, we silenced specific gene expression in the DRG by lentiviral vectors in the monosodium urate (MSU)-induced ankle GA mouse model and evaluated alterations in the inflammatory response. In vitro, primary macrophages were used to investigate the neural impact on M1/M2 subtype polarization, proinflammatory cytokine production and downstream endothelial damage. Mechanism by which macrophage inflammation is induced in the DRG was evaluated by Western blot, immunofluorescence, and immunoprecipitation. Results: We found that secreted frizzled-related protein 2 (sFRP2) was the most upregulated gene in dorsal root ganglion (DRG) neurons in response to monosodium urate (MSU) deposition. Injection of LV-sFRP2-shRNA into the L4 and L5 DRG significantly suppressed inflammatory cell infiltration and M1 polarization in the synovial membrane, attenuating hyperalgesia and ankle swelling in the GA mouse model. In vitro, DRG neurons-derived sFRP2 promoted M1 polarization and macrophage migration, thereby upregulating the production of proinflammatory cytokines and preventing endothelial apoptosis. Furthermore, DRG-derived sFRP2 activated the nuclear factor (NF)-κB pathway by destabilizing the β-catenin and p65 complex. Conclusion: We demonstrated the involvement of a sensory neuron-macrophage axis in GA pathology that was regulated by sFRP2 expression in a paracrine manner. Targeting increased sFRP2 expressions in DRG provide novel insights for future GA research in both pain alleviation and treatment of gout inflammation.

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Stefin B alleviates the gouty arthritis in mice by inducing the M2 polarization of macrophages.

Publications

Stefin B alleviates the gouty arthritis in mice by inducing the M2 polarization of macrophages.

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