Elastin fragments induce IL-1β upregulation via NF-κB pathway in melanoma cells

In a previous work, we reported the influence of elastin fragments (EFs) on matrix metalloproteinases-2 and -14 expression and activation in melanoma cells in vitro. We hypothesized that EFs might also modulate expression of other mediators involved during melanoma progression. Therefore we investigated the contribution of EFs on IL-1 beta expression, a cytokine playing a key role in melanoma cells activation. Our results evidenced that high tumorigenic melanoma cells (M(3)Da cells) treated with EFs led to IL-1 beta mRNA and protein upregulation. The effects of EFs on M3Da cells were found to be mediated by receptor (spliced galactosidase) occupancy, as being suppressed by lactose and reproduced by cell stimulation with the VGVAPG peptide. Binding of EFs to their receptor induced a rapid activation of extracellular signal-regulated kinase 1/2; and p38 mitogen-activated protein kinase pathways. However, these pathways were not associated with IL-1 beta mRNA upregulation by EFs. Concomitantly, we demonstrated that EFs stimulation induced NF-kappa B nuclear translocation and DNA binding on IL-1 beta promoter region whereas inhibition of NF-kappa B with the specific chemical inhibitor SN-50 or by overexpression of NF-kappa B, the endogenous inhibitor of NF-kappa B pathway, totally abolished EFs-mediated IL-1 beta mRNA overexpression. These results demonstrate that EFs induce NF-kappa B activation, leading to IL-1 beta upregulation in invasive melanoma cells.