J Invest Dermatol 2006,
PMID: 16675961
Debret, Romain; Le Naour, Richard R; Sallenave, Jean-Michel; Deshorgue, Aurelie; Hornebeck, William G; Guenounou, Moncef; Bernard, Philippe; Antonicelli, Frank D
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-1beta expression, a cytokine playing a key role in melanoma cells activation. Our results evidenced that high tumorigenic melanoma cells (M3Da cells) treated with EFs led to IL-1beta 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-1beta mRNA upregulation by EFs. Concomitantly, we demonstrated that EFs stimulation induced NF-kappaB nuclear translocation and DNA binding on IL-1beta promoter region whereas inhibition of NF-kappaB with the specific chemical inhibitor SN-50 or by overexpression of IkappaB, the endogenous inhibitor of NF-kappaB pathway, totally abolished EFs-mediated IL-1beta mRNA overexpression. These results demonstrate that EFs induce NF-kappaB activation, leading to IL-1beta upregulation in invasive melanoma cells.
Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System, Melanoma, Skin Neoplasms
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Text Mining Data
EFs → extracellular signal regulated kinase 1/2: "
Binding of
EFs to their receptor
induced a rapid activation of
extracellular signal regulated kinase 1/2 ; and p38 mitogen activated protein kinase pathways
"
IL-1beta → EFs: "
However, these pathways were not associated with IL-1beta mRNA upregulation by EFs
"
EFs ⊣ IL-1beta: "
Concomitantly, we demonstrated that EFs stimulation induced NF-kappaB nuclear translocation and DNA binding on IL-1beta promoter region whereas inhibition of NF-kappaB with the specific chemical inhibitor SN-50 or by overexpression of IkappaB, the endogenous inhibitor of NF-kappaB pathway, totally abolished EFs mediated IL-1beta mRNA overexpression
"
NF-kappaB ⊣ IL-1beta: "
Concomitantly, we demonstrated that EFs stimulation induced NF-kappaB nuclear translocation and DNA binding on IL-1beta promoter region whereas inhibition of NF-kappaB with the specific chemical inhibitor SN-50 or by overexpression of IkappaB, the endogenous inhibitor of NF-kappaB pathway, totally abolished EFs mediated IL-1beta mRNA overexpression
"
EFs → NF-kappaB: "
Concomitantly, we demonstrated that EFs stimulation induced NF-kappaB nuclear translocation and DNA binding on IL-1beta promoter region whereas inhibition of NF-kappaB with the specific chemical inhibitor SN-50 or by overexpression of IkappaB, the endogenous inhibitor of NF-kappaB pathway, totally abolished EFs mediated IL-1beta mRNA overexpression
"
EFs → NF-kappaB: "
These results demonstrate that EFs induce NF-kappaB activation, leading to IL-1beta upregulation in invasive melanoma cells
"
Manually curated Databases
No curated data.