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Transcriptional and posttranscriptional regulation and endocytosis were involved in zinc oxide nanoparticle-induced interleukin-8 overexpression in human bronchial epithelial cells.
- Source :
-
Cell biology and toxicology [Cell Biol Toxicol] 2014 Apr; Vol. 30 (2), pp. 79-88. Date of Electronic Publication: 2014 Feb 20. - Publication Year :
- 2014
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Abstract
- Inhaled zinc oxide nanoparticles (ZnO-NPs) can induce lung inflammation through released inflammatory mediators, such as interleukin 8 (IL-8), from airways. However, the mechanisms underlying ZnO-NP-induced IL-8 gene expression have not been fully characterized. The transcription inhibitor actinomycin D (Act D) and the BEAS-2B cells stably overexpressing wild-type or mutated IL-8 promoter at the NFκB or C/EBPβ binding site were used to determine the involvement of transcriptional mechanisms. The effect of ZnO-NPs on IL-8 mRNA stability was examined using mRNA decay assay. The phagocytosis inhibitor cytochalasin B (CB) was utilized to define the role of endocytosis in ZnO-NP-induced IL-8 expression. In addition, the solubility of ZnO-NPs in culture medium was assessed using atomic absorption spectroscopy. Exposure to ZnO-NPs significantly increased the expression of IL-8 mRNA and protein in a dose-dependent manner. Pretreatment with Act D blocked ZnO-NP-induced IL-8 expression. Both NFκB and C/EBPβ transcription factors were required for ZnO-NP-induced IL-8 transcription. mRNA decay assay showed that ZnO-NP stimulation delayed IL-8 mRNA degradation in BEAS-2B cells. Pretreatment of BEAS-2B cells with CB blocked ZnO-NP-induced IL-8 expression by 30 %. Exposure to ZnO-NPs induced IL-8 gene expression through transcriptional activation and mRNA stabilization. Internalization of nanoparticles was partially involved in ZnO-NP-induced IL-8 expression.
- Subjects :
- Bronchi cytology
CCAAT-Enhancer-Binding Protein-beta genetics
Cell Line
Cytochalasin B pharmacology
Dactinomycin pharmacology
Endocytosis
Epithelial Cells cytology
Gene Expression Regulation drug effects
Humans
Interleukin-8 genetics
NF-kappa B genetics
Nucleic Acid Synthesis Inhibitors pharmacology
Promoter Regions, Genetic
Protein Processing, Post-Translational
Protein Synthesis Inhibitors pharmacology
RNA Stability drug effects
RNA, Messenger biosynthesis
RNA, Messenger genetics
Transcription, Genetic
Transcriptional Activation drug effects
Transcriptional Activation genetics
Bronchi metabolism
Epithelial Cells metabolism
Interleukin-8 biosynthesis
Metal Nanoparticles
Zinc Oxide pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-6822
- Volume :
- 30
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell biology and toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 24554449
- Full Text :
- https://doi.org/10.1007/s10565-014-9270-9