Cartilage degeneration and
inflammation are important features of
rheumatoid arthritis (RA). Chondrocyte
inflammation and apoptosis have been increasingly demonstrated to be related to cartilage decomposition. In this study, we analyzed the protective role of
kallistatin against RA and its associated mechanisms. We obtained in vitro and in vivo RA models using IL-1β and heat-inactivated Mycobacterium tuberculosis, respectively. Our results showed that
kallistatin mitigated IL-1β-mediated chondrocyte apoptosis and inhibited the synthesis of ECM-degrading generation, like
matrix metalloproteinase (
MMP)-3/13 and a
disintegrin and
metalloproteinase with
thrombospondin motifs (ADAMTS)-4/5, in IL-1β-mediated chondrocytes. Furthermore,
kallistatin markedly suppressed IL-1β-mediated
inflammation while decreasing the levels of inflammatory factors and mediators via the NF-κB pathway. Daily administration of
kallistatin reduced the expression levels of
PGE2, TNF-α, IL-1β, and
IL-6. Histochemical analysis revealed that the
kallistatin-treated rats exhibited reduced RA severity compared with control mice. In summary,
kallistatin suppressed IL-1β-mediated
inflammation in chondrocytes via the NF-κB pathway. Administration of
kallistatin remarkably inhibited RA development, accompanied by reduced
inflammation and apoptosis. Therefore,
kallistatin administration can be used as a candidate therapeutic strategy for RA.