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Pyrroloquinoline Quinone Decelerates Rheumatoid Arthritis Progression by Inhibiting Inflammatory Responses and Joint Destruction via Modulating NF-κB and MAPK Pathways

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Abstract

Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient and antioxidant and has been reported to exert potent immunosuppressive effects. However, the therapeutically potential of PQQ on rheumatoid arthritis (RA) has not been explored. In the present study, the anti-inflammatory effects of PQQ were investigated in interleukin (IL)-1β-treated SW982 cells, a RA-like fibroblast-like synoviocytes (FLSs) injury model. Our observations showed that pretreatment with PQQ significantly inhibited the expression of matrix metalloproteinase (MMP)-1 and MMP-3 and suppressed the production of proinflammatory mediators such as TNF-α and IL-6 in IL-1β-treated SW982 cells. The nuclear translocation of nuclear factor kappa B (NF-κB) and the phosphorylation level of p65, p38, and JNK MAP kinase pathways were also inhibited by PQQ in IL-1β-stimulated SW982 cells. To further confirm the therapeutic effects of PQQ on RA in vivo, a collagen-induced arthritis (CIA) model was used. Mice treated with PQQ demonstrated marked attenuation of arthritic symptoms based on histopathology and clinical arthritis scores. These results collectively suggested that PQQ might be a promising therapeutic agent for alleviating the progress of RA.

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Acknowledgments

This work were supported by the Clinical Medicine Special Funds of Jiangsu Province (BL2014059), Postgraduate Technology Innovation Project of Nantong University (YKS14004), National Basic Research Program of China (973 Program, No.2012CB822104), National Natural Science Foundation of China (31170766), National Natural Science Foundation of China (81171140), Key Project Natural Science Foundation of Jiangsu University and College (No.11KJA310002), Nantong City Social Development Projects funds (HS2012032), and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China

    Zhongbing Liu, Chi Sun, Ran Tao, Xinbao Xu, Libin Xu, Youhua Wang & Dongmei Zhang

  2. Department of Orthopaedics, Traditional Chinese Medical Hospital of Nantong City, Nantong, 226001, China

    Hongbing Cheng

  3. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, China

    Dongmei Zhang

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  1. Zhongbing Liu
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Correspondence to Youhua Wang or Dongmei Zhang.

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Liu, Z., Sun, C., Tao, R. et al. Pyrroloquinoline Quinone Decelerates Rheumatoid Arthritis Progression by Inhibiting Inflammatory Responses and Joint Destruction via Modulating NF-κB and MAPK Pathways. Inflammation 39, 248–256 (2016). https://doi.org/10.1007/s10753-015-0245-7

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  • DOI: https://doi.org/10.1007/s10753-015-0245-7

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