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Identification of LPS‐inducible genes downregulated by ubiquinone in human THP‐1 monocytes
Author(s) -
Schmelzer Constance,
Döring Frank
Publication year - 2010
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.93
Subject(s) - thp1 cell line , gene expression , proinflammatory cytokine , gene , downregulation and upregulation , transcription factor , biology , microbiology and biotechnology , monocytic leukemia , cell culture , biochemistry , inflammation , genetics , immunology
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 ≤ 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 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 NFκB 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.