1 Cellular Functional Nanobiomaterials Group, Research Center for Functional Materials, National Institute for Materials Science (NIMS), Tsukuba, Ibaraki, Japan
2 Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan
3 Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
4 Glycobiology Laboratory, Nagaoka University of Technology, 1603-1 Kamitomiokamachi, Nagaoka, Niigata 940-2137, Japan
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.
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.
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.
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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* Address correspondence to this author at the Cellular Functional Nanomaterials Group, Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan; Tel: 81-29-860-4505; E-mail: firstname.lastname@example.org