ZnO nanoparticles induce TNF-alpha expression via ROS-ERK-Egr-1 pathway in human keratinocytes
- Authors
- Jeong, Sang Hoon; Kim, Hee Joo; Ryu, Hwa Jeong; Ryu, Woo In; Park, Yoon-Hee; Bae, Hyun Cheol; Jang, Yeon Sue; Son, Sang Wook
- Issue Date
- 12월-2013
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- Egr-1; ERK; ZnO nanoparticles; Nanotoxicity
- Citation
- JOURNAL OF DERMATOLOGICAL SCIENCE, v.72, no.3, pp.263 - 273
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF DERMATOLOGICAL SCIENCE
- Volume
- 72
- Number
- 3
- Start Page
- 263
- End Page
- 273
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/101528
- DOI
- 10.1016/j.jdermsci.2013.08.002
- ISSN
- 0923-1811
- Abstract
- Background: The area of nanotechnology continues to expand rapidly and zinc oxide (ZnO) nanoparticles (NPs) are widely being used in cosmetics and sunscreens. Although ZnO-NPs are considered materials that can potentially cause skin inflammation, the underlying mechanisms remain elusive. Objective: The aim of this study was to investigate the signaling pathways of a cutaneous inflammatory response induced by ZnO-NPs. ZnO-NPs increased the early growth response-1 (Egr-1) expression, promoter activity and its nuclear translocation in HaCaT cells. Methods: HaCaT cells and primary keratinocytes were exposed to ZnO NPs over a range of doses and time course. Protein levels and mRNA levels of Egr-1 and mitogen-activated protein kinase (MAPK) were measured by Western blot and ELISA, respectively. As an in vivo study, ZnO-NPs were applicated on mouse skin, and immunohistochemical stain with TNE-alpha and Egr-1 was done. Results: ZnO-NPs activated extracellular signal-regulated kinase (ERK) of MAPK pathways. The upregulation of Egr-1 expression by ZnO-NPs stimulation was found to be inhibited by an ERK inhibitor, but by neither c-Jun-N-terminal kinase (JNK) nor p38 inhibitor. Antioxidative N-acetyl-cysteine (NAC) strongly inhibited the level of Egr-1 and phosphorylated ERR expression in ZnO-NPs treated cells. ZnO NPs also increased tumor necrosis factor (TNE)-alpha expression and secretion, which were inhibited by the blockade of Egr-1 expression. Conclusions: The present study demonstrated that ZnO-NPs might induce inflammatory response via ROS-ERK-Egr-1 pathway in human keratinocytes. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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