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Inflammation suppression by dexamethasone via inhibition of CD147-mediated NF-κB pathway in collagen-induced arthritis rats

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Abstract

Dexamethasone (Dex) exhibits broad-spectrum anti-inflammatory effects in chronic destructive rheumatoid arthritis. We present in vivo and in vitro evidence supporting the preventive effects and underlying mechanisms of Dex on collagen-induced arthritis (CIA)-induced synovial injuries. After successful induction of CIA, Wistar rats were administered Dex intraperitoneally (1 mg/kg) three times a week for more than 2 weeks. In vivo, paw swelling, arthritis scores, and histological evaluations were analyzed to determine the therapeutic effects of Dex on the progression of arthritis. In vitro, CIA fibroblast-like synoviocytes (FLSs) were treated for 48 h with vehicle (control group), 10 ng/mL IL-1α (IL-1α group), 10 ng/mL IL-1α + 10 μM Dex (Dex group), or 10 ng/mL IL-1α + 10 μg/mL anti-CD147 antibody (anti-CD147 group). Evaluations of FLSs proliferation, cell cycle, migration, gene expression of Cyclin D1, p27, p57, interleukin (IL)-1β, IL-6, IL-17, tumor necrosis factor (TNF)-α, CD147, CypB, matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13, ROS generation, protein expression of NF-κB and CD147, and translocation of NF-κB p65 were all conducted. The in vivo results showed that arthritis intensity was attenuated in the Dex-treated group. The in vitro findings demonstrated that treatment with Dex induced G0/G1 arrest and suppressed proliferation, migration, gene expression of IL-1β, IL-6, IL-17, TNF-α, CD147, CypB, MMP-3, MMP-9, and MMP-13, ROS generation and protein expression of NF-κB and CD147. Translocation of NF-κB p65 was inhibited by both Dex and anti-CD147 monoclonal antibody treatment. We offer molecular evidence of the anti-rheumatism efficacy Dex through hindrance to CD147, splendidly stabilization of the oxidative stress by downregulating the NF-κB signaling pathway.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81874011, 81572104 and 81301531) and the Shanghai Municipal Science and Technology Commission (Innovation Grant Nos. 18140903502).

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Authors and Affiliations

  1. Departments of Pharmacy, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

    Qishan Wang, Bingxin Xu, Kaijian Fan, Jing Wu & Tingyu Wang

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  1. Qishan Wang
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  2. Bingxin Xu
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  3. Kaijian Fan
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  4. Jing Wu
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Contributions

All authors contributed the study conceptualization and design. Methodology, project administration, validation and data curation were performed by QW, BX, KF and JW. Original draft preparation was written by QW and review and editing were conducted by TW. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Tingyu Wang.

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All animal experiment procedures were approved by the Animal Ethics Committee of Shanghai Ninth People’s Hospital.

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Wang, Q., Xu, B., Fan, K. et al. Inflammation suppression by dexamethasone via inhibition of CD147-mediated NF-κB pathway in collagen-induced arthritis rats. Mol Cell Biochem 473, 63–76 (2020). https://doi.org/10.1007/s11010-020-03808-5

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