Background and Objectives: Silver nanoparticles (AgNPs) have a dual effect showing both inflammatory and anti-inflammatory effects; however, the molecular mechanism of their anti-inflammatory effect is not clearly understood. In this study, we investigated the effect of AgNPs on the inflammatory response. Methods: We induced an inflammatory response in a lung epithelial cell line using tumor necrosis factor-α (TNFα) as an in vitro inflammatory model. Then the effect of AgNPs on the TNFα-induced inflammatory response was observed. Results: The mRNA expression of pro-inflammatory cytokines (IL-1β and IL-18) showed upregulation of IL-1β by AgNPs alone. However, AgNPs reduced the TNFα-induced upregulation of IL-1β and IL-18. AgNPs reduced the TNFα-induced NF-KB response, reactive oxygen species (ROS) generation, Nod Like Receptor Family-Pyrin domain containing 3 (NLRP3) gene expression, and caspase-1 activation, indicating that the anti-inflammatory effect of AgNPs was by inhibition of both NF-KB transcriptional and inflammasome pathways. Conversely, AgNPs alone induced the activation of both NF-KB transcriptional and inflammasome pathways, suggesting their involvement in the molecular mechanism of the inflammatory effect of AgNPs. Conclusion: Altogether, these findings show that two different pathways are involved in the molecular mechanism of both the dose-dependent inflammatory effect of AgNPs alone and the anti-inflammatory effect of AgNPs against the TNFα-induced inflammatory response. Understanding this mechanism will help to improve the medical applications of AgNPs and suggest their potential as a TNFα inhibitor to treat TNFα-induced inflammatory diseases.
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