Identification of LPS-inducible genes downregulated by ubiquinone in human THP-1 monocytes

作者：Schmelzer Constance; Doering Frank

来源：Biofactors, 2010, 36(3): 222-228.

DOI：10.1002/biof.93

• CoQ10
• gene expression
• inflammation
• monocytes
• LPS

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 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 NF kappa B 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. Gene Ontology (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., CNOT(4) and STK(4)). Three genes were either related to NF kappa B 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.

• 出版日期2010-6