Identification of LPS-inducible genes downregulated by ubiquinone in human THP-1 monocytes.
Coenzyme Q(10) (CoQ(10)) 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 CoQ(10) on gene expression have been observed. To reveal putative effects of Q(10) 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 <or= 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 NFkappaB pathway and confirmed our applied in vitro stimulation model. Moreover, 33 LPS-sensitive genes have been identified to be significantly downregulated by Q(10)-treatment between a factor of 1.32 and 1.85. GeneOntology (GO) analysis revealed for the Q(10)-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 NFkappaB transcription factor activity (ERC1), cytokinesis (DIAPH2), or modulation of oxidative stress (MSRA). In conclusion, our data provide evidence that Q(10) downregulates LPS-inducible genes in the monocytic cell line THP-1. Thus, the previously described effects of Q(10) on the reduction of proinflammatory mediators might be due to its antioxidant impact on gene expression.
Schmelzer
Constance
C
Institute of Human Nutrition and Food Science, Molecular Prevention, Christian-Albrechts-University of Kiel, Germany.
Döring
Frank
F
D002460:Cell Line; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018977:Micronutrients / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D014451:Ubiquinone / Q000494:pharmacology*
D008070:Lipopolysaccharides; D018977:Micronutrients; D014451:Ubiquinone