Mycoplasma bovis induces matrix metalloproteinase-3 expression in bovine synovial cells via up-regulation of interleukin-1β expression in mononuclear cells

Abstract

Mycoplasma bovis causes chronic arthritis in calves, presenting as osteolysis in affected joints. Matrix metalloproteinase-3 (MMP-3), an enzyme involved in cartilage degradation, is produced by synovial cells. Production of this proteinase is regulated by interleukin (IL)-1β, which is produced by mononuclear cells. Both factors are known to play important roles in osteolysis in human autoimmune and bacterial arthritis. However, the pathophysiology of Mycoplasma arthritis (MA) has not been elucidated. In this study, we evaluated the levels of MMP-3 and IL-1β in synovial fluid (SF) from MA calves and examined the effect of IL-1β on MMP-3 expression in bovine synovial cells in vitro. Levels of MMP-3 and IL-1β in SF from MA calves were significantly higher than those of clinically healthy calves. Mycoplasma bovis induced significant increases in the expression of IL-1β mRNA and protein in mononuclear cells, compared with cells not exposed to M. bovis. Interestingly, the supernatant of mononuclear cells stimulated with M. bovis contained high levels of IL-1β, which induced higher expression of MMP-3 mRNA and protein in synovial cells than direct stimulation by M. bovis. Recombinant bovine IL-1β also induced increased MMP-3 mRNA and protein expression in synovial cells. Our results indicate that M. bovis induces IL-1β expression by bovine mononuclear cells, and this cytokine then promotes MMP-3 production by synovial cells. These findings suggest that MMP-3 and IL-1β are key factors in the development of osteolysis in MA calves.