Abstract
Poly(propyleneimine) dendrimers fully surface-modified with disaccharide moieties (maltose, cellobiose, and lactose) designed to mimic natural lectin receptor ligands were tested for their bioactivity in two myeloid cell lines: THP-1 and HL-60. Depending on the sugar modification, we observed variable activation of NF-κB, AP-1, and NF-AT signaling pathways: lactose-coated dendrimers had the strongest impact on marker gene expression and most signaling events with the notable exception of NF-κB activation in THP-1 cells. The two cell lines showed an overall similar pattern of transcription factor and gene expression activation upon treatment with glycodendrimers, suggesting the involvement of galectin and C-type lectin receptor types. An important result of this action was the overexpression of CD40 and IL8 genes, potentially leading to an activated, proinflammatory phenotype in the monocyte/macrophage cell lineage. These pharmacodynamic characteristics of glycodendrimers need to be taken into account during their pharmaceutical applications both in drug delivery and direct immunomodulation.
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