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

Inflammation. 2016 Feb;39(1):248-256. doi: 10.1007/s10753-015-0245-7.

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.

Keywords: P65; SW982; collagen-induced arthritis (CIA); inflammatory; pyrroloquinoline quinone (PQQ).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • Ankle Joint / pathology*
  • Antioxidants / therapeutic use*
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Rheumatoid / drug therapy*
  • Cell Line
  • Humans
  • Inflammation / drug therapy
  • Inflammation / prevention & control
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / pharmacology
  • Interleukin-6 / biosynthesis
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Matrix Metalloproteinase 1 / biosynthesis
  • Matrix Metalloproteinase 3 / biosynthesis
  • Mice
  • Mice, Inbred DBA
  • PQQ Cofactor / therapeutic use*
  • Phosphorylation / drug effects
  • Synovial Membrane / cytology
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antioxidants
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • RELA protein, human
  • TNF protein, human
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • PQQ Cofactor
  • p38 Mitogen-Activated Protein Kinases
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • MMP1 protein, human
  • Matrix Metalloproteinase 1