The Effect of BAY 60-7550 on Rheumatoid Arthritis via the Regulation of the Nrf2/HO-1 Signaling Pathway in DBA/1J Mice

Bay 60-7550 (BAY), a selective and potent PDE2 inhibitor, is potentially useful for enhancing cAMP/cGMP-mediated object and spatial memory consolidation.BAY has been widely known to have anti-cancer, anti-oxidant and anti-inflammatory effects.However, the effect of BAY on rheumatoid arthritis (RA) is still not well-known.In this study, a collagen-induced arthritis (CIA) model in DBA/1J mice was induced by primary immunization with Bovine type II collagen (BCII) and Complete Freund's adjuvant (CFA), and by a booster injection with BCII and Incomplete Freund's adjuvant (IFA).The hallmark symptoms of RA which were evaluated by von frey test and grip strength test were significantly alleviated in the CIA + BAY group.Moreover, the bone erosion, cartilage destruction, and synovial hyperplasia were improved in the CIA + BAY group compared to the CIA group.The mRNA and protein expressions of RA-related inflammatory cytokines were remarkably increased in the CIA group but these were significantly decreased in the CIA + BAY group.In particular, BAY significantly regulated the mRNA of Nrf2/HO-1.In conclusion, BAY could alleviate bone erosion and inflammation in CIA mice by regulating Nrf2/HO-1 signal.This study suggests that BAY will be a potential drug as a treatment for rheumatoid arthritis.