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

Abstract

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.

Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes

“…Genome-scale transcriptional responses of protein-coding genes following lipopolysaccharide (LPS)-induced activation of the innate immune response in human monocytes and monocytic cell lines have been extensively studied using both microarrays1 and serial analysis of gene expression23. These studies have clearly demonstrated the induction of many members of proinflammatory cytokines (for example, IL1β, CXCL8, IL6 and tumor necrosis factor alpha ( TNFα )), chemokines and cell surface markers in response to Toll-like receptor 4 (TLR4) signalling3.…”

Ubiquinol reduces gamma glutamyltransferase as a marker of oxidative stress in humans

“…CoQ 10 is a known modulator of gene expression [4,5] and inflammatory processes [7-9]. Because the reduced form of CoQ 10 , ubiquinol, is a potent antioxidant that protects lipids, DNA and proteins from oxidative damage [12-14], we examined the effect of Q 10 H 2 supplementation on both serum GGT and AST activity as potential markers of oxidative stress.…”

“…Plasma C-reactive protein (CRP) concentrations were measured using a latex enhanced nephelometric assay run on a BN II hematology analyzer (Dade Behring, Marburg, Germany). Microarray experiments using the Affymetrix human genome U133 plus 2.0 GeneChip® were performed as previously described [5] with RNA samples from CD14-positive monocytes obtained from three volunteers before (T 0 ) and after (T 14 ) supplementation with ubiquinol.…”

Coenzyme Q10 Status as a Determinant of Muscular Strength in Two Independent Cohorts

“…Furthermore, CoQ 10 could act as an antioxidant, preventing oxidative damage of lipids, proteins and DNA [7,8]. Moreover, CoQ 10 has been identified as a modulator of gene expression [9, 10] and is necessary for the function of uncoupling proteins [11] and pyrimidine biosynthesis [12]. The percentage of the oxidized form of CoQ increases with age, indicating a decreased anti-oxidative capacity of aged individuals [13].…”