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Activation of Inflammation/NF- κB Signaling in Infants Born to Arsenic-Exposed Mothers

Activation of Inflammation/NF- κB Signaling in Infants Born to Arsenic-Exposed Mothers Published: Nov 23, 2007 - DOI: 10.1371/journal.pgen.0030207

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Activation of Inflammation/NF- κB Signaling in Infants Born to Arsenic-Exposed Mothers

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  1. Activation of Inflammation/NF-κBSignaling in Infants Bornto Arsenic-Exposed Mothers Published: Nov 23, 2007 - DOI: 10.1371/journal.pgen.0030207 Rebecca C Fry equal contributor, PanidaNavasumrit equal contributor, ChandniValiathan equal contributor, J. Peter Svensson, Bradley J Hogan, ManlinLuo, Sanchita Bhattacharya, KrittineeKandjanapa, SumitraSoontararuks, SumonthaNookabkaew, ChulabhornMahidol, MathurosRuchirawat, Leona D Samson This study has permitted a better understanding of the impact of maternal arsenic exposure. Constant exposure to arsenic-contaminated water is an important public health hazard around the world. The results of this study put in evidence the alarming gene expression changes in new-born babies to arsenic-exposed mothers with in utero robust activation of inflammation, cell proliferation, stress and apoptosis with increased mortality rates. M e t h o d : This study was conducted in the Ron Pibul and Bangkok districts of Thailand in an arsenic contaminated region attributed to tin mining from 1960s to 1980s. Brigitte-Karaja dyzAthlandys Figure 1. Gene Expression Signatures Predict Arsenic Exposure in Tests Population. (B) Expression values are mean centered with high relative expression indicated in red and low relative expression indicated in blue. Apoptosis/stress response (C) * * * * Cell adhesion Signal transduction Figure 2. Prenatal Arsenic Exposure Results in Robust Genome-Wide Changes response in the foetus and acts as an inflammatory stimulus That activates NF-kB, playing a critical role in inflammation-driven tumour progression (Luo,2003) (D) Glucose transport Lipid metabolism Transcription Figure 3. Sub-networks of Prenatal Arsenic-Modulated Gene Products (D) TNF-a–associated network composed of eight core members of the potential gene biomarkers for arsenic exposure. Biomarker genes with binding sites for MTF transcription factor are indicated. Proteins in red (C) An EGR-1, OSM, JUNB focused sub-network highlights numerous biological processes modulated in response to arsenic. Proteins encoded by 11 potential gene biomarkers for arsenic exposure are indicated with a *. ▀ Down-regulated - - - - - - - Indirect intervention ▀ Cytokinine ◊ ◊ Enzyme ▼▼Kinase Trapezoid / Trapezoid Transporter ○ ○ Other ▀Up-regulated _____________ Direct intervention ▲Phosphatase █ G protein coupled receptor Oval horizontal Transcriptional regulator Oval vertical Transmembranereceptor Globally, millions of people exposed to arsenic are highly contaminated and suffering. ◙ Because arsenic targets widely disperse enzymes reactions, it affects all organ systems according to the Agency for Toxic Substances. R e f e r e n c e : Luo, J.L. et al. (2003) Inhibition of NF-kappaB in cancer cells converts inflammation-induce tumor growth mediated by TNF alpha to TRAIL-mediated tumors regression. Cancer cell, 2004:6:297-305 PubMed.

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