Interleukin-1[beta] triggers matrix metalloprotease-3 expression through p65/RelA activation in melanoma cells

Melanoma shows highly aggressive behavior (i.e., local invasion and metastasis). Matrix metalloprotease-3 (MMP-3), a zinc-dependent endopeptidase, degrades several extracellular substrates and contributes to local invasion by creating a microenvironment suitable for tumor development. Here, we report that interleukin-1[beta] (IL-1[beta]) triggers the MMP-3 expression in canine melanoma cells. The activity of MMP-3 in the culture supernatant was increased in IL-1[beta]-treated melanoma cells. IL-1[beta] time- and dose-dependently provoked the mRNA expression of MMP-3. IL-1[beta] induced the migration of melanoma cells; however, this migration was attenuated by UK356618, an MMP-3 inhibitor. When the cells were treated with the nuclear factor-[kappa]B (NF-[kappa]B) inhibitor TPCA-1, the inhibition of MMP-3 expression was observed. In IL-1[beta]-treated cells, the phosphorylation both of p65/RelA and p105 was detected, indicating NF-[kappa]B pathway activation. In p65/RelA-depleted melanoma cells, IL-1[beta]-mediated mRNA expression of MMP-3 was inhibited, whereas this reduction was not observed in p105-depleted cells. These findings suggest that MMP-3 expression in melanoma cells is regulated through IL-1[beta]-mediated p65/RelA activation, which is involved in melanoma cell migration.