PMID- 26371860 OWN - NLM STAT- MEDLINE DCOM- 20160724 LR - 20161125 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 28 IP - 2 DP - 2015 Oct TI - Activation of NRF2 pathway in spleen, thymus as well as peripheral blood mononuclear cells by acute arsenic exposure in mice. PG - 1059-67 LID - S1567-5769(15)30083-7 [pii] LID - 10.1016/j.intimp.2015.08.025 [doi] AB - Arsenic has already been demonstrated to activate the nuclear factor erythroid 2-related factor 2 (NRF2) in many different organs and cell lines. The present study tried to explore the expression of NRF2 pathway by acute arsenic exposure in immune system in vivo. Our results showed that treatment with arsenic (sodium arsenite, 5, 10 and 20mg/kg, intra-gastrically) increased the expression of NRF2 and its downstream targets heme oxygenase-1 (HO-1), glutathione-S-transferase (GST), glutamate-cysteine ligase (GCL) and glutathione reductase (GR) consistently in spleen, thymus, as well as peripheral blood mononuclear cells (PBMCs), as early as treatment from 6h. Arsenic was also detected to up-regulate the mRNA levels of Hmox1, NAD(P)H: quinine oxidoreductase 1 (Nqo1), Gclc and Gclm in spleen and thymus. Besides, we detected the enhancement of Kelch-like ECH-associated protein (KEAP1) expression in these immune organs and immunocytes. What's more, our results also found the imbalanced oxidative redox status under the circumstances that arsenic activated NRF2 pathway, reflected by the generation of lipid peroxidation, as well as the reduction of antioxidative capacities in both spleen and thymus. Taken together, our results here strongly suggested the expression and activation of NRF2 pathway by acute arsenic exposure in immune system in vivo. Further studies are being investigated to explore the possible roles and functions of NRF2 pathway stimulation in the regulation of immune responses of this metalloid. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Duan, Xiaoxu AU - Duan X AD - Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China. FAU - Li, Jinlong AU - Li J AD - Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China. FAU - Zhang, Yang AU - Zhang Y AD - Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China. FAU - Li, Wei AU - Li W AD - Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China. FAU - Zhao, Lu AU - Zhao L AD - Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China. FAU - Nie, Huifang AU - Nie H AD - Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China. FAU - Sun, Guifan AU - Sun G AD - Environment and Non-Communicable Diseases Research Center, School of Public Health, China Medical University, Shenyang 110013, China. FAU - Li, Bing AU - Li B AD - Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China. Electronic address: libing@mail.cmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150911 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Cytoskeletal Proteins) RN - 0 (Hazardous Substances) RN - 0 (Keap1 protein, mouse) RN - 0 (Kelch-Like ECH-Associated Protein 1) RN - 0 (Membrane Proteins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.14.14.18 (Hmox1 protein, mouse) RN - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone)) RN - EC 1.6.5.2 (Nqo1 protein, mouse) RN - N712M78A8G (Arsenic) SB - IM MH - Adaptor Proteins, Signal Transducing/genetics/metabolism MH - Animals MH - Arsenic/*administration & dosage/toxicity MH - Cytoskeletal Proteins/genetics/metabolism MH - Environmental Exposure/adverse effects MH - Female MH - Hazardous Substances/*administration & dosage/toxicity MH - Heme Oxygenase-1/genetics/metabolism MH - Kelch-Like ECH-Associated Protein 1 MH - Leukocytes, Mononuclear/immunology MH - Lipid Peroxidation MH - Membrane Proteins/genetics/metabolism MH - Mice MH - Mice, Inbred C57BL MH - NAD(P)H Dehydrogenase (Quinone)/genetics/metabolism MH - NF-E2-Related Factor 2/*metabolism MH - Oxidation-Reduction MH - Signal Transduction MH - Spleen/*physiology MH - Thymus Gland/*physiology OTO - NOTNLM OT - Arsenic OT - Immune OT - NRF2 OT - Peripheral blood mononuclear cells OT - Spleen OT - Thymus EDAT- 2015/09/16 06:00 MHDA- 2016/07/28 06:00 CRDT- 2015/09/16 06:00 PHST- 2015/04/14 00:00 [received] PHST- 2015/08/19 00:00 [revised] PHST- 2015/08/21 00:00 [accepted] PHST- 2015/09/16 06:00 [entrez] PHST- 2015/09/16 06:00 [pubmed] PHST- 2016/07/28 06:00 [medline] AID - S1567-5769(15)30083-7 [pii] AID - 10.1016/j.intimp.2015.08.025 [doi] PST - ppublish SO - Int Immunopharmacol. 2015 Oct;28(2):1059-67. doi: 10.1016/j.intimp.2015.08.025. Epub 2015 Sep 11.