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Inhibition of P2X4 Suppresses Joint Inflammation and Damage in Collagen-Induced Arthritis

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Abstract

Recent data have shown that the purinergic receptor P2X4 plays key roles in inflammatory responses. We evaluated whether P2X4 inhibition could affect the development of arthritis and autoimmunity in collagen-induced arthritis (CIA) model. P2X4 antisense oligonucleotide (asODN) was injected intravenously via tail vein into the CIA mice to selectively inhibit P2X4 expression daily for 14 days. P2X4 asODN treatment reduced the clinical score of CIA in mice. P2X4 asODN also decreased the levels of serum IL-1β, TNF-α, IL-6, and IL-17. P2X4 asODN treatment significantly inhibited synovial inflammation and joint destruction. P2X4 asODN treatment also suppressed the NLR family, pyrin domain containing 1 (NLRP1) inflammasome activation in CIA mice and synovial cells of human rheumatoid arthritis. These data show that P2X4 asODN confers a therapeutic benefit on CIA. Inhibition of the NLRP1 inflammasome signaling pathway is the underlying mechanism of action.

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Conflict of interest

All authors declare no conflicts of interest in this study.

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Authors and Affiliations

  1. Department of Rheumatology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, Shandong, China

    Faxin Li & Yuxia Ma

  2. Department of Hematology, Jinan Central Hospital Affiliated to Shandong University, Lixia District, 105 Jiefang Road, Jinan, 250013, Shandong, China

    Nongjian Guo

  3. Department of Orthopedics, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, Shandong, China

    Bin Ning

  4. Department of Clinical Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, Shandong, China

    Yan Wang

  5. Department of Radiology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, Shandong, China

    Liqing Kou

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  1. Faxin Li
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  2. Nongjian Guo
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  3. Yuxia Ma
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  4. Bin Ning
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  5. Yan Wang
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Correspondence to Nongjian Guo.

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Li, F., Guo, N., Ma, Y. et al. Inhibition of P2X4 Suppresses Joint Inflammation and Damage in Collagen-Induced Arthritis. Inflammation 37, 146–153 (2014). https://doi.org/10.1007/s10753-013-9723-y

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  • DOI: https://doi.org/10.1007/s10753-013-9723-y

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