The Reduced Form of Coenzyme Q10 Decreases the Expression of Lipopolysaccharide-Sensitive Genes in Human THP-1 Cells

Monocytes are key players in inflammatory processes that are triggered by lipopolysaccharide (LPS), the major outer membrane component of Gram-negative bacteria. The present study in human monocytic THP-1 cells was designed in order to identify LPS-inducible genes that are down-regulated by the reduced form of coenzyme Q(10) (ubiquinol, Q(10)H(2)). For this purpose, THP-1 cells were incubated with 10 mu M Q(10)H(2) for 24 hours. Subsequently, cells were stimulated for 4 hours with 1 mu g/mL LPS, and the resulting gene expression levels were determined using microarrays. Fourteen LPS-inducible genes were identified to be significantly (P <= .05) down-regulated by Q(10)H(2) pretreatment between a factor of 1.32 and 1.65. The strongest effect of Q(10)H(2) incubation was found for the nuclear receptor coactivator 2 gene (NCOA2). Gene ontology terms revealed for the Q(10)H(2)-sensitive genes an involvement in, e. g., signal transduction processes (centaurin, delta 1; NCOA2; pleckstrin and Sec7 domain containing 3; protein phosphatase 2, regulatory subunit B [B56], gamma isoform), transcriptional regulation (NCOA2; POU domain, class 2, transcription factor 1; ETS variant gene 3), and cell proliferation pathways (hypothetical protein FLJ36090, epidermal growth factor receptor pathway substrate 15). In conclusion, we provide evidence in THP-1 cells that Q(10)H(2) modulates LPS-induced gene expression.