Zinc Oxide Nanoparticles Suppress LPS-Induced NF-κB Activation by Inducing A20, a Negative Regulator of NF-κB, in RAW 264.7 Macrophages

Zinc contained in solar salt and bamboo salt plays a critical role in various immune responses. Zinc oxide is a source of zinc, and recently it has been reported that zinc oxide nanoparticles (ZO-NP) more effectively decrease allergic inflammatory reactions than zinc oxide bulk material. The aim of this work was to investigate the regulatory effect of ZO-NP on interferon (IFN)-gamma plus lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. ZO-NP (0.1-10 mu g/mL) did not affect cell viability but toxicity was evident at a ZO-NP concentration of 100 mu g/mL. ZO-NP (10 mu g/mL) inhibited the IFN-gamma plus LPS-induced production of nitric oxide and the protein expressions of inducible nitric oxide synthase and cyclooxygenase-2. The productions of inflammatory cytokines, such as, interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha were increased by IFN-gamma plus LPS but down-regulated by ZO-NP treatment. Furthermore, the up-regulations of IL-1 beta and TNF-alpha mRNAs by IFN-gamma plus LPS were reduced by ZO-NP at low (0.1 mu g/mL) and high (10 mu g/mL) concentrations. ZO-NP (0.1, 1, and 10 mu g/mL) inhibited the nuclear translocation of nuclear factor-kappa B by blocking I kappa Ba phosphorylation and degradation. In addition, ZO-NP induced the expression of A20, a zinc finger protein and negative regulator of NF-kappa B. In conclusion, the present study demonstrated that ZO-NP offer a potential means of treating inflammatory diseases.