Pro-inflammatory responses of RAW264.7 macrophages when treated with ultralow concentrations of silver, titanium dioxide, and zinc oxide nanoparticles

Highlights: • Ultralow levels of common nanoparticles exist in environment and consumer products. • Common nanoparticles at ultralow levels induce mild pro-inflammation by macrophages. • The nanoparticles are cytotoxic only at high doses. - Abstract: To cellular systems, nanoparticles are considered as foreign particles. Upon particles and cells contact, innate immune system responds by activating the inflammatory pathway. However, excessive inflammation had been linked to various diseases ranging from allergic responses to cancer. Common nanoparticles, namely silver, titanium dioxide, and zinc oxide exist in the environment as well as in consumer products at ultralow level of 10⁻⁶–10⁻³ μg mL⁻¹. However, so far the risks of such low NPs concentrations remain unexplored. Therefore, we attempted to screen the pro-inflammatory responses after ultralow concentration treatments of the three nanoparticles on RAW264.7 macrophages, which are a part of the immune system, at both cellular and gene levels. Even though cytotoxicity was only observed at nanoparticles concentrations as high as 10 μg mL⁻¹, through the level of NF-κB and upregulation of pro-inflammatory genes, we observed activation of the induction of genes encoding pro-inflammatory cytokines starting already at 10⁻⁷ μg mL⁻¹. This calls for more thorough characterization of nanoparticles in the environment as well as in consumer products to ascertain the health and safety of the consumers and living systems in general