Reactive Oxygen Species Enhance TLR10 Expression in the Human Monocytic Cell Line THP-1
| Autor: | Hyo Eun Park, Donghee Kim, Tae Yang Jang, Yeon-Ju Kim, Hyun Sook Koh, Jae-Young Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Biology
Catalysis Article Inorganic Chemistry lcsh:Chemistry Downregulation and upregulation Cell Line Tumor Toll-like receptor10 reactive oxygen species hypoxia monocytes Humans THP1 cell line RNA Messenger Physical and Theoretical Chemistry Molecular Biology Transcription factor lcsh:QH301-705.5 Spectroscopy chemistry.chemical_classification Reactive oxygen species Organic Chemistry NF-kappa B General Medicine Hydrogen Peroxide NFKB1 Oxidants Molecular biology Cell Hypoxia Computer Science Applications Cell biology chemistry lcsh:Biology (General) lcsh:QD1-999 Cell culture Toll-Like Receptor 10 Second messenger system Intracellular |
| Zdroj: | International Journal of Molecular Sciences; Volume 11; Issue 10; Pages: 3769-3782 International Journal of Molecular Sciences, Vol 11, Iss 10, Pp 3769-3782 (2010) International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms11103769 |
| Popis: | We investigated TLR10 expression in human monocytes, THP-1 cells, cultured in hypoxia (3% O(2)). Levels of both TLR10 mRNA and protein in THP-1 cells cultured in hypoxia were significantly higher than those cultured in normoxia (20% O(2)). We examined intracellular reactive oxygen species (ROS) content in hypoxic cells, and TLR10 expression in cells treated with hydrogen peroxide (H(2)O(2)), to determine whether the increase in TLR10 expression observed with hypoxia was due to an increase in intracellular ROS levels. We found that the level of intracellular ROS in cells subject to hypoxia was significantly higher than in normoxia. Experiments with ROS synthesis inhibitors revealed that hypoxia induced ROS production is mainly due to NADPH oxidase activity. TLR10 mRNA expression was increased by treatment with H(2)O(2) at concentrations ranging from 50 to 250 μM. We screened the TLR10 promoter and found putative binding sites for transcription factors (TFs), such as NF-κB, NF-AT and AP-1. Next, we examined TF activities using a luciferase reporter assay. Activities of NF-κB, NF-AT and AP-1 in the cells treated with H(2)O(2) were significantly higher than in untreated cells. The experiment with TF inhibitors revealed that ROS-induced upregulation of TLR10 expression is mainly due to NF-κB activation. Overall, our results suggest that hypoxia or ROS increase TLR10 expression in human monocytes and the transcriptional activities of NF-κB are involved in this process. Therefore, it is suggested that ROS produced by various exogenous stimuli may play a crucial role in the regulation of expression and function of TLR10 as second messengers. |
| Databáze: | OpenAIRE |
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