ZnO nanoparticles induce TNF-α expression via ROS-ERK-Egr-1 pathway in human keratinocytes

Sang Hoon Jeong, Hee Joo Kim, Hwa Jeong Ryu, Woo In Ryu, Yoon Hee Park, Hyun Cheol Bae, Yeon Sue Jang, Sang Wook Son

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


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 TNF-α and Egr-1 was done. Results: ZnO-NPs activated extracellular signal-regulated kinase (ERK) of MAPK pathways. The up-regulation 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 ERK expression in ZnO-NPs treated cells. ZnO NPs also increased tumor necrosis factor (TNF)-α 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.

Original languageEnglish
Pages (from-to)263-273
Number of pages11
JournalJournal of Dermatological Science
Issue number3
Publication statusPublished - 2013 Dec


  • ERK
  • Egr-1
  • Nanotoxicity
  • ZnO nanoparticles

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


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