Oxidative stress by layered double hydroxide nanoparticles via an SFK-JNK and p38-NF-κB signaling pathway mediates induction of interleukin-6 and interleukin-8 in human lung epithelial cells

Abstract

Anionic nanoclays are layered double hydroxide nanoparticles (LDH-NPs) that have been shown to exhibit toxicity by inducing reactive oxidative species and a proinflammatory mediator in human lung epithelial A549 cells. However, the molecular mechanism responsible for this LDH-NP-induced toxicity and the relationship between oxidative stress and inflammatory events remains unclear. In this study, we focused on intracellular signaling pathways and transcription factors induced in response to oxidative stress caused by exposure to LDH-NPs in A549 cells. Mitogen-activated protein kinase (MAPK) cascades, such as extracellular signal-regulated kinase, c-Jun-N-terminal kinase (JNK), and p38, were investigated as potential signaling mechanisms responsible for regulation of oxidative stress and cytokine release. Src family kinases (SFKs), which are known to mediate activation of MAPK, together with redox-sensitive transcription factors, including nuclear factor kappa B and nuclear factor-erythroid 2-related factor-2, were also investigated as downstream events of MAPK signaling. The results obtained suggest that LDH-NP exposure causes oxidative stress, leading to expression of antioxidant enzymes, such as catalase, glucose reductase, superoxide dismutase, and heme oxygenase-1, via a SFK-JNK and p38-nuclear factor kappa B signaling pathway. Further, activation of this signaling was also found to regulate release of inflammatory cytokines, including interleukin-6 and interleukin-8, demonstrating the inflammatory potential of LDH-NP.

Toxicity assessment of hydroxyapatite nanoparticles in rat liver cell model in vitro

“…Likewise, it was determined that HAP NP exposure caused oxidative stress, leading to expression of antioxidant enzymes, such as catalase, superoxide dismutase (SOD), and heme oxygenase-1, via a Src family kinase (SFK)-JNK and p38-NF-κB signaling pathway in human lung epithelial A549 cells. 53 The measurement of SOD generation also showed that HAP NPs decreased the total SOD of cellular levels in C6 glioma cells. 54 Again, in an in vivo study, a dose-dependent decrease in the activity of glutathione peroxidase was observed in dermally HAP NP exposed rats.…”

A Simple Route to the Complexation of Lutein with Reduced Graphene Oxide Nanocarriers and Antioxidant Protection Against Blue Light

“…In principle, the mitochondrial electron transport chain is a major source of intracellular ROS. 74,75 Moreover, in the respiratory chain, blue light is absorbed directly by molecules, such as flavin and cytochrome oxidase, which [76][77][78][79] The process of mitochondrial redistribution with morphological changes in ARPE-19 cells under blue light irradiation has been reported previously; the mitochondria of RPE cells irradiated at a wavelength of ~ 400 nm were observed to be denatured and low level in distribution and were observed to be prominent only in the perinuclear region. 80 The same condition was reported in a similar study in which a generation of long and large mitochondria exhibited a reduction in their membrane potential for ARPE-19 cells.…”

Cytotoxicity, Uptake Behaviors, and Oral Absorption of Food Grade Calcium Carbonate Nanomaterials

“…It seems that CaCO 3 nanoparticles can damage the cell membrane and consequently induce ROS, but these cytotoxic effects are not severe to affect cell prolliferation. It was reported that layered double hydroxide nanoparticles did not block cell proliferation up to 500 μg/mL, but caused ROS generation and LDH release [ 26 , 27 ]. Slightly high cytotoxicity of food nano CaCO 3 is likely to be associated with surface roughenss resulting from the grinding process of sea shells as shown in AFM images and height profile in Figure 1 B.…”