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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

Authors Choi SJ, Paek HJ, Yu J

Received 2 February 2015

Accepted for publication 18 March 2015

Published 29 April 2015 Volume 2015:10(1) Pages 3217—3229

DOI https://doi.org/10.2147/IJN.S82061

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Thomas J Webster

Soo-Jin Choi, Hee-Jeong Paek, Jin Yu

Department of Food Science and Technology, Seoul Women’s University, Seoul, Republic of Korea

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.

Keywords: layered double hydroxide, mitogen-activated protein kinases, Src family kinases, nuclear factor kappa B, oxidative stress, inflammatory cytokine

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