Dp44mT regulates the levels of inflammatory mediators through blocking NF-κB nuclear translocation in LPS-stimulated RAW 264.7 macrophages

Abstract

Inflammation is increased by infection with pathogens such as viruses, bacteria, and parasites. High levels of inflammatory mediators and infiltration of macrophages into inflammatory lesions were reported in severe inflammatory diseases. Here, the aim of this study was to evaluate an anti-inflammatory activity of di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Dp44mT (1–100 ng/mL) had no effect on viability of RAW 264.7 macrophages. Dp44mT (100 ng/mL) significantly reduced LPS-induced release of nitric oxide and expression of inducible nitric oxide synthase and cyclooxygenase-2. A significant upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-6 by LPS stimulation was downregulated by treatment with Dp44mT. Dp44mT blocked activation of nuclear factor-κB by the interruption of IκBα phosphorylation. Dp44mT suppressed the phagocytosis. Furthermore, administration of Dp44mT significantly reduced the serum levels of TNF-α and IL-6 in LPS-treated mice without side effects. In conclusion, these results indicate that Dp44mT has an anti-inflammatory activity and may be of therapeutic significant for the prevention and treatment of inflammatory diseases.