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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. [ABSTRACT FROM AUTHOR]

Karyopherin-α2 (KPNA2) functions as an adaptor that transports several proteins to the nucleus. We investigated the function and possible mechanisms of KPNA2 involved in rheumatoid arthritis (RA). Western blotting and immunohistochemistry showed the protein expression of KPNA2 increased in synovial tissue of RA patients compared with the healthy controls. Double immunofluorescent staining indicated that KPNA2 co-localized with T cells, macrophage-like synoviocytes, fibroblast-like synoviocytes, and neutrophils in synovial tissue of RA patients. Moreover, the expression of KPNA2 in SW982 cells was increased in a time-dependent manner in response to TNFα stimulation. Both Western blotting and immunofluorescent staining assay revealed the co-localization of KPNA2 and P65 and their translocation from cytoplasma in TNFα-treated SW982 cells. Furthermore, knocking down the expression of KPNA2 by siRNA inhibited TNFα-induced expression of IL-6, MMP-1, and MMP-13 and, more importantly, decreased the P65 phosphorylation in SW982 cells. We therefore suggested that KPNA2 may play a key role in the inflammation process of RA via NF-κB P65 signal transduction pathway. [ABSTRACT FROM AUTHOR]