Functions of coenzyme Q10 in inflammation and gene expression

Clinical studies demonstrated the efficacy of Coenzyme Q(10) (CoQ(10)) as an adjuvant therapeutic in cardiovascular diseases, mitochondrial myopathies and neurodegenerative diseases. More recently, expression profiling revealed that Coenzyme Q(10) (COQ(10)) influences the expression of several hundred genes. To unravel the functional connections of these genes, we performed a text mining approach using the Genomatix BiblioSphere. We identified signalling pathways of G-protein coupled receptors, JAK/STAT, and Integrin which contain a number of CoQ(10) sensitive genes. Further analysis suggested that IL5, thrombin, vitronectin, vitronectin receptor, and C-reactive protein are regulated by CoQ(10) via the transcription factor NF kappa B1. To test this hypothesis, we studied the effect of CoQ(10) on the NF kappa B1-dependent pro-inflammatory cytokine TNF-alpha. As a model, we utilized the murine macrophage cell lines RAW264.7 transfected with human apolipoprotein E3 (apoE3, control) or pro-inflammatory apoE4. In the presence of 2.5 mu M or 75 mu M CoQ(10) the LPS-induced TNF-alpha response was significantly reduced to 73.3 +/- 1 2.8% and 74.7 +/- 8.9% in apoE3 or apoE4 cells, respectively. Therefore, the in silico analysis as well as the cell culture experiments suggested that CoQ(10) exerts anti-inflammatory properties via NF kappa B1-dependent gene expression.