The effect of gallium nitrate on synoviocyte MMP activity

Gallium, a group IIIa metal salt, has been demonstrated to be an effective immunosuppressive agent. Gallium has also been shown to inhibit the production of inflammatory cytokines, such as IL-1beta, produced by macrophage-like cells in vitro. To further characterize the effects of gallium on the inflammatory process, we examined the effects of gallium nitrate on matrix metalloproteinase (MMP) activity utilizing the rabbit synoviocyte cell line HIG-82. HIG-82 cells were incubated with IL-1beta and TPA, with and without increasing concentrations of gallium nitrate. Conditioned medium was collected and assayed for MMP activity using a synthetic substrate and substrate gel zymography. IL-1beta and TPA alone induced MMP activity in HIG-82 cells. A dose-dependent inhibition of IL-1beta and TPA stimulated MMP activity by gallium nitrate at increasing concentrations was observed. This study demonstrates that gallium nitrate can inhibit the activity of MMPs and may be useful as a modulator of inflammation in arthritis.