Acicular, but not globular, titanium dioxide nanoparticles stimulate keratinocytes to produce pro‐inflammatory cytokines

Abstract

Titanium dioxide (TiO2 ) nanoparticles, widely used for daily products, are believed to be biologically inert, but they may cause adverse effects on cells, presumably depending on the particle size and shape. One of the critical targets of TiO2 particles is epidermal keratinocytes, and their initial response to TiO2 may be production of pro-inflammatory cytokines. We therefore investigated the effects of four types of TiO2 particles on cytokine expression/production by real-time reverse transcription polymerase chain reaction and enzyme-linked immunoassay. The TiO2 particles included three acicular types, FTL-100 (length, 1.68 μm; diameter, 130 nm), FTL-200 (2.86, 210) and FTL-300 (5.15, 270), and one globular type, PT-301 (diameter, 270 nm). Normal human epidermal keratinocytes (NHEK) were cultured with each of the TiO2 particles. During cultivation, the acicular forms of TiO2 were seen by scanning electron microscopy to be internalized by NHEK. The three acicular particles increased the mRNA expressions and supernatant productions of interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor-α and IL-8 in particle number-dependent manners, whereas globular PT-301 had very weak activity. Thus, TiO2 particles may induce skin inflammation depending on the size and shape, providing knowledge on their health usage.

Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease

“…Although initial studies reported that TiO 2 did not penetrate the stratum corneum, a recent study indicated that the cubic and about 25nm size sample was cytotoxic to human epidermal keratinocytes 306 . Similarly, acicular TiO 2 ‐NP is shown to interact with human epidermal keratinocytes, induce secretion of pro‐inflammatory cytokines and disrupt the skin barrier by altering cell junctions 307 . The intestinal toxicity of NPs is less known, cationic liposome NPs containing ZnO, silver, aluminum, and nickel, as well as TiO 2 and SiO 2 NPs, accumulate across the intestinal epithelial barrier and then translocate by endocytosis by the M‐cell, or by disrupting the integrity of the cell membrane, or by phagocytosis by macrophages 305,308 .…”

The Roles of Autophagy and the Inflammasome during Environmental Stress-Triggered Skin Inflammation

“…TiO 2 NPs can cause several adverse effects on mammalian cells, including ROS production [62,63], DNA damage responses [64], proliferation, and the induction of apoptosis [65,66]. Hiroike et al suggested that acicular, but not globular TiO 2 NPs stimulate keratinocytes to produce pro-inflammatory cytokines such as IL-1α, IL-1β, IL-6, TNF-α, and IL-8 [67]. The increased production of these cytokines leads to cutaneous inflammatory responses, as typically seen in contact dermatitis [68].…”

The complex cascade of cellular events governing inflammasome activation and IL-1β processing in response to inhaled particles

“…However, other immune cells such as dendritic cells or monocytes are also able to release large amount of mature IL-1β. In addition, structural cells of various body compartments exposed to particles secrete, although to a lesser extent, mature IL-1β [ 11 – 18 ]. For instance, primary rat epithelial lung cells, cardiomyocytes, cardiofibroblasts and mesothelial cells also respond to particles by priming and activating inflammasome [ 13 , 16 , 19 – 21 ].…”