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• W2065054017 abstract "Inflammation is a major risk factor for carcinogenesis in patients affected by chronic colitis, yet the molecular mechanisms underlying the progression from chronic inflammation to cancer are not completely understood. Activation of the Toll-like receptor 4 (TLR4)-NFκB signaling axis is associated with inflammation. Thus, we hypothesized that inhibition of TLR4-NFκB signaling might help in limiting inflammatory responses and inflammation-induced oncogenesis. In this work, we studied the effects of a TLR4-interacting surfactant protein A-derived (SPA4) peptide on lipopolysaccharide (LPS)-induced TLR4-NFκB signaling and cancer progression. We first characterized this peptide for its ability to bind the TLR4 ligand-LPS and for physico-chemical characteristics. Inflammation was induced by challenging the colon cancer SW480 cells with Escherichia coli LPS. Cells were then treated with varying amounts of the SPA4 peptide. Changes in the expression of TLR4, interleukin (IL)-1β and IL-6, in intracellular NFκB-related signal transducers (IKBα, p65, phosphorylated IKBα, phosphorylated p65, RelB, COX-2) as well as in the transcriptional activity of NFκB were studied by immunocytochemistry, immunoblotting and NFκB reporter assay, respectively. Simultaneously, the effects on LPS-induced cell migration and invasion were determined. We found that the SPA4 peptide does not bind to LPS. Rather, its binding to TLR4 inhibits the LPS-induced phosphorylation of p65, production of IL-1β and IL-6, activity of NFκB, migration and invasion of SW480 cells. In conclusion, our results suggest that the inhibition of TLR4-NFκB signaling by a TLR4-binding peptide may help for the treatment of chronic inflammation and prevention of inflammation-induced cancer in patients with colitis." @default.
• W2065054017 created "2016-06-24" @default.
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• W2065054017 date "2012-12-01" @default.
• W2065054017 modified "2023-10-06" @default.
• W2065054017 title "A TLR4-interacting peptide inhibits lipopolysaccharide-stimulated inflammatory responses, migration and invasion of colon cancer SW480 cells" @default.
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• W2065054017 doi "https://doi.org/10.4161/onci.22089" @default.
• W2065054017 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3525605" @default.
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• W2065054017 hasPublicationYear "2012" @default.
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