학술논문

Identification of LPS-inducible genes downregulated by ubiquinone in human THP-1 monocytes.
Document Type
Article
Source
Biofactors. 2010, Vol. 36 Issue 3, p222-228. 7p. 1 Diagram, 3 Graphs.
Subject
*UBIQUINONES
*GENE expression
*INFLAMMATION
*MONOCYTES
*ENDOTOXINS
Language
ISSN
0951-6433
Abstract
Coenzyme Q10 (CoQ10) is an obligatory element in the respiratory chain and functions as a potent antioxidant of lipid membranes. More recently, anti-inflammatory effects as well as an impact of CoQ10 on gene expression have been observed. To reveal putative effects of Q10 on LPS-induced gene expression, whole genome expression analysis was performed in the monocytic cell line THP-1. Thousand one hundred twenty-nine and 710 probe sets have been identified to be significantly (P ≤ 0.05) up and downregulated in LPS-treated cells when compared with controls, respectively. Text mining analysis of the top 50 LPS upregulated genes revealed a functional connection in the NFκB pathway and confirmed our applied in vitro stimulation model. Moreover, 33 LPS-sensitive genes have been identified to be significantly downregulated by Q10-treatment between a factor of 1.32 and 1.85. GeneOntology (GO) analysis revealed for the Q10-sensitve genes a primary involvement in protein metabolism (e.g., HERC1 and EPS15), cell proliferation (e.g., CCDC100 and SMURF1), and transcriptional processes (e.g., CNOT4 and STK4). Three genes were either related to NFκB transcription factor activity (ERC1), cytokinesis (DIAPH2), or modulation of oxidative stress (MSRA). In conclusion, our data provide evidence that Q10 downregulates LPS-inducible genes in the monocytic cell line THP-1. Thus, the previously described effects of Q10 on the reduction of proinflammatory mediators might be due to its antioxidant impact on gene expression. [ABSTRACT FROM AUTHOR]