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ZnO nanoparticles induce TNF-α expression via ROS-ERK-Egr-1 pathway in human keratinocytes
- Source :
- Journal of Dermatological Science. 72:263-273
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
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 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.
- Subjects :
- Keratinocytes
MAPK/ERK pathway
Cell Survival
p38 mitogen-activated protein kinases
Dermatology
Biochemistry
Cell Line
Microscopy, Electron, Transmission
Western blot
medicine
Humans
Extracellular Signal-Regulated MAP Kinases
Protein kinase A
Molecular Biology
Early Growth Response Protein 1
medicine.diagnostic_test
Tumor Necrosis Factor-alpha
Chemistry
Kinase
technology, industry, and agriculture
Molecular biology
Oxidative Stress
HaCaT
Nanoparticles
Tumor necrosis factor alpha
Inflammation Mediators
Zinc Oxide
Signal transduction
Reactive Oxygen Species
Signal Transduction
Subjects
Details
- ISSN :
- 09231811
- Volume :
- 72
- Database :
- OpenAIRE
- Journal :
- Journal of Dermatological Science
- Accession number :
- edsair.doi.dedup.....70431c00b50db5c3d06e2de199df7bbf