Global effects of inorganic arsenic on gene expression profile in human macrophages

Bourdonnay, Emilie; Morzadec, Claudie; Sparfel, Lydie; Galibert, Marie‐Dominique; Jouneau, S.; Martin-Chouly, Corinne; Fardel, Olivier; Vernhet, Laurent

doi:10.1016/j.molimm.2008.08.268

Cited by 44 publications

(28 citation statements)

References 31 publications

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“…Prior studies of macrophage transcriptome indicate that changes in MDM gene expression in response to external stimuli (numbers of genes; inflammatory, anti-inflammatory) are highly variable and dependent upon the particle (inert or pathogen) ingested and nature of the exposure [91]–[94]. After interaction or infection with L. (V.) panamensis , results of the current report suggest that the early responses (0 to 4 hours) lead to up-regulation of transcripts contributing to an inflammatory state of the host macrophage.…”

Section: Discussionmentioning

confidence: 99%

Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response

et al. 2012

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BackgroundPrevious findings indicate that susceptibility to Leishmania (Viannia) panamensis infection of monocyte-derived macrophages from patients and asymptomatically infected individuals were associated with the adaptive immune response and clinical outcome.Methodology/Principal FindingsTo understand the basis for this difference we examined differential gene expression of human monocyte-derived macrophages following exposure to L. (V.) panamensis. Gene activation profiles were determined using macrophages from healthy volunteers cultured with or without stationary phase promastigotes of L. (V.) panamensis. Significant changes in expression (>1.5-fold change; p<0.05; up- or down-regulated) were identified at 0.5, 4 and 24 hours. mRNA abundance profiles varied over time, with the highest level of activation occurring at earlier time points (0.5 and 4 hrs). In contrast to observations for other Leishmania species, most significantly changed mRNAs were up- rather than down-regulated, especially at early time points. Up-regulated transcripts over the first 24 hours belonged to pathways involving eicosanoid metabolism, oxidative stress, activation of PKC through G protein coupled receptors, or mechanism of gene regulation by peroxisome proliferators via PPARα. Additionally, a marked activation of Toll-receptor mediated pathways was observed. Comparison with published microarray data from macrophages infected with L. (Leishmania) chagasi indicate differences in the regulation of genes involved in signaling, motility and the immune response.ConclusionsResults show that the early (0.5 to 24 hours) human monocyte-derived macrophage response to L. (Viannia) panamensis is not quiescent, in contrast to published reports examining later response times (48–96 hours). Early macrophage responses are important for the developing cellular response at the site of infection. The kinetics and the mRNA abundance profiles induced by L. (Viannia) panamensis illustrate the dynamics of these interactions and the distinct biologic responses to different Leishmania species from the outset of infection within their primary host cell.

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Section: Discussionmentioning

confidence: 99%

Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response

et al. 2012

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“…We hypothesized that in utero exposure to arsenic would be associated with altered epigenome-wide methylation after controlling for cell mixture. Based on experimental evidence that arsenic alters the development, activation and proliferation of T-cells, [26][27][28][29][30][31][32][33][34][35][36][37] we further hypothesized that prenatal arsenic exposure would independently influence the immune response, which would be associated with altered leukocyte subpopulations in cord blood.…”

Section: Introductionmentioning

confidence: 99%

Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood

et al. 2014

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“…Environmental exposures, such as to arsenic or cadmium, can disrupt gene expression (Andrew et al 2008; Bourdonnay et al 2009; Castillo et al 2012; Cheng et al 2012; Hossain et al 2012; Su et al 2006). Findings suggest that the health effects of environmental exposures, including exposure to metals, could be mediated in part by epigenetic mechanisms (Arita and Costa 2009; Reichard and Puga 2010; Ren et al 2011; Smeester et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Association of Global DNA Methylation and Global DNA Hydroxymethylation with Metals and Other Exposures in Human Blood DNA Samples

Téllez-Plaza

Tang

Shang

et al. 2014

Environ Health Perspect

105

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Background: The association between human blood DNA global methylation and global hydroxymethylation has not been evaluated in population-based studies. No studies have evaluated environmental determinants of global DNA hydroxymethylation, including exposure to metals.Objective: We evaluated the association between global DNA methylation and global DNA hydroxymethylation in 48 Strong Heart Study participants for which selected metals had been measured in urine at baseline and DNA was available from 1989–1991 (visit 1) and 1998–1999 (visit 3).Methods: We measured the percentage of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in samples using capture and detection antibodies followed by colorimetric quantification. We explored the association of participant characteristics (i.e., age, adiposity, smoking, and metal exposure) with both global DNA methylation and global DNA hydroxymethylation.Results: The Spearman’s correlation coefficient for 5-mC and 5-hmC levels was 0.32 (p = 0.03) at visit 1 and 0.54 (p < 0.001) at visit 3. Trends for both epigenetic modifications were consistent across potential determinants. In cross-sectional analyses, the odds ratios of methylated and hydroxymethylated DNA were 1.56 (95% CI: 0.95, 2.57) and 1.76 (95% CI: 1.07, 2.88), respectively, for the comparison of participants above and below the median percentage of dimethylarsinate. The corresponding odds ratios were 1.64 (95% CI: 1.02, 2.65) and 1.16 (95% CI: 0.70, 1.94), respectively, for the comparison of participants above and below the median cadmium level. Arsenic exposure and metabolism were consistently associated with both epigenetic markers in cross-sectional and prospective analyses. The positive correlation of 5-mC and 5-hmC levels was confirmed in an independent study population.Conclusions: Our findings support that both epigenetic measures are related at the population level. The consistent trends in the associations between these two epigenetic modifications and the characteristics evaluated, especially arsenic exposure and metabolism, suggest the need for understanding which of the two measures is a better biomarker for environmental epigenetic effects in future large-scale epidemiologic studies.Citation: Tellez-Plaza M, Tang WY, Shang Y, Umans JG, Francesconi KA, Goessler W, Ledesma M, Leon M, Laclaustra M, Pollak J, Guallar E, Cole SA, Fallin MD, Navas-Acien A. 2014. Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples. Environ Health Perspect 122:946–954; http://dx.doi.org/10.1289/ehp.1306674

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Global effects of inorganic arsenic on gene expression profile in human macrophages

Cited by 44 publications

References 31 publications

Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response

Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response

Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood

Association of Global DNA Methylation and Global DNA Hydroxymethylation with Metals and Other Exposures in Human Blood DNA Samples

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