Interleukin-1β 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.

Automated summary

IL-1 beta triggers the expression of MMP-3 in melanoma cells, which is involved in cell migration.