Back to Journals » International Journal of Nanomedicine » Volume 10 » Issue 1

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 S, Paek H, Yu J

Received 2 February 2015

Accepted for publication 18 March 2015

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


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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Other articles by this author:

The fate of calcium carbonate nanoparticles administered by oral route: absorption and their interaction with biological matrices

Lee JA, Kim MK, Kim HM, Lee JK, Jeong J, Kim YR, Oh JM, Choi SJ

International Journal of Nanomedicine 2015, 10:2273-2293

Published Date: 23 March 2015

Pharmacokinetics, tissue distribution, and excretion of zinc oxide nanoparticles

Baek M, Chung HE, Yu J, Lee JA, Kim TH, Oh JM, Lee WJ, Paek SM, Lee JK, Jeong J, Choy JH, Choi SJ

International Journal of Nanomedicine 2012, 7:3081-3097

Published Date: 26 June 2012

Readers of this article also read:

Effective small interfering RNA delivery in vitro via a new stearylated cationic peptide

Chen BL, Pan R, Askhatova D, Chen P

International Journal of Nanomedicine 2015, 10:3303-3314

Published Date: 2 May 2015

Formation of curcumin nanoparticles via solution-enhanced dispersion by supercritical CO2

Zhao Z, Xie M, Li Y, Chen A, Li G, Zhang J, Hu H, Wang X, Li S

International Journal of Nanomedicine 2015, 10:3171-3181

Published Date: 29 April 2015

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010