Involvement of Nrf2 activation in the upregulation of S100A9 by exposure to inorganic arsenite

Sumi,Daigo; Shimizu,Yuri; Himeno,Seiichiro

doi:10.3892/ijmm.2012.1185

Involvement of Nrf2 activation in the upregulation of S100A9 by exposure to inorganic arsenite

Authors:
- Daigo Sumi
- Yuri Shimizu
- Seiichiro Himeno
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Affiliations: Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
Published online on: November 16, 2012 https://doi.org/10.3892/ijmm.2012.1185
Pages: 259-264

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Abstract

This study examined whether S100A8 and S100A9, which comprise a complex called calprotectin, are upregulated by exposure to sodium arsenite [As(III)] in nine lines of human-derived cells. HaCaT skin keratinocyte cells, U937 leukemic monocyte cells, and UROtsa urothelial cells showed increased mRNA levels of S100A8 and S100A9 after a 2-week exposure to As(III). To understand the mechanisms regulating S100A9 upregulation in response to As(III), we tested S100A9 promoter-dependent luciferase activity in HaCaT cells transfected with S100A9 promoter (-1000/+429)-fused luciferase cDNA. The results indicated that exposure to As(III) stimulated S100A9 promoter-dependent luciferase activity. In addition, the transcription NF-E2-related factor 2 (Nrf2) was strongly activated in HaCaT cells exposed to As(III). Since two putative antioxidant response elements were found in the S100A9 promoter (ARE1, 5'-ACAGGCAGGG-3' from -897 to -887; ARE2, 5'-ATCTTCCGGAG-3' from -78 to -67), we constructed deletion mutants of each ARE on S100A9 promoter-fused luciferase cDNA. The results indicated that ARE2 is the responsible element for the activation of S100A9 transcription in response to As(III). This report is the first to demonstrate that As(III) enhanced S100A8 and S100A9 expression in human-derived cells and As(III)-induced S100A9 expression is dependent on Nrf2 activation.

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1	Engel RR, Hopenhayn-Rich C, Receveur O and Smith AH: Vascular effects of chronic arsenic exposure: a review. Epidemiol Rev. 16:184–209. 1994.PubMed/NCBI
2	Tseng WP, Chu HM, How SW, Fong JM, Lin CS and Yeh S: Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. J Natl Cancer Inst. 40:453–463. 1968.PubMed/NCBI
3	Kozul CD, Hampton TH, Davey JC, et al: Chronic exposure to arsenic in the drinking water alters the expression of immune response genes in mouse lung. Environ Health Perspect. 117:1108–1115. 2009. View Article : Google Scholar : PubMed/NCBI
4	Liao WT, Yu CL, Lan CC, et al: Differential effects of arsenic on cutaneous and systemic immunity: focusing on CD4⁺ cell apoptosis in patients with arsenic-induced Bowen’s disease. Carcinogenesis. 30:1064–1072. 2009. View Article : Google Scholar : PubMed/NCBI
5	Banerjee N, Banerjee S, Sen R, et al: Chronic arsenic exposure impairs macrophage functions in the exposed individuals. J Clin Immunol. 29:582–594. 2009. View Article : Google Scholar : PubMed/NCBI
6	Shimizu Y, Fujishiro H, Matsumoto K, Sumi D, Satoh M and Himeno S: Chronic exposure to arsenite induces S100A8 and S100A9 expression in rat RBL-2H3 mast cells. J Toxicol Sci. 36:135–139. 2011. View Article : Google Scholar : PubMed/NCBI
7	Ehrchen JM, Sunderkotter C, Foell D, Vogl T and Roth J: The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer. J Leukoc Biol. 86:557–566. 2009. View Article : Google Scholar : PubMed/NCBI
8	Nacken W, Roth J, Sorg C and Kerkhoff C: S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity. Microsc Res Tech. 60:569–580. 2003. View Article : Google Scholar : PubMed/NCBI
9	Kerkhoff C, Nacken W, Benedyk M, Dagher MC, Sopalla C and Doussiere J: The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase activation by interaction with p67^phox and Rac-2. FASEB J. 19:467–469. 2005.PubMed/NCBI
10	Kerkhoff C, Sorg C, Tandon NN and Nacken W: Interaction of S100A8/S100A9-arachidonic acid complexes with the scavenger receptor CD36 may facilitate fatty acid uptake by endothelial cells. Biochemistry. 40:241–248. 2001. View Article : Google Scholar : PubMed/NCBI
11	Loser K, Vogl T, Voskort M, et al: The Toll-like receptor 4 ligands Mrp8 and Mrp14 are crucial in the development of autoreactive CD8⁺ T cells. Nat Med. 16:713–717. 2010. View Article : Google Scholar : PubMed/NCBI
12	Itoh K, Tong KI and Yamamoto M: Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radic Biol Med. 36:1208–1213. 2004. View Article : Google Scholar : PubMed/NCBI
13	Aono J, Yanagawa T, Itoh K, et al: Activation of Nrf2 and accumulation of ubiquitinated A170 by arsenic in osteoblasts. Biochem Biophys Res Commun. 305:271–277. 2003. View Article : Google Scholar : PubMed/NCBI
14	Kumagai Y and Sumi D: Arsenic: signal transduction, transcription factor, and biotransformation involved in cellular response and toxicity. Annu Rev Pharmacol Toxicol. 47:243–262. 2007. View Article : Google Scholar : PubMed/NCBI
15	Fusenig NE and Boukamp P: Multiple stages and genetic alterations in immortalization, malignant transformation, and tumor progression of human skin keratinocytes. Mol Carcinog. 23:144–158. 1998. View Article : Google Scholar : PubMed/NCBI
16	Rossi MR, Masters JR, Park S, et al: The immortalized UROtsa cell line as a potential cell culture model of human urothelium. Environ Health Perspect. 109:801–808. 2001. View Article : Google Scholar : PubMed/NCBI
17	Cheng P, Corzo CA, Luetteke N, et al: Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein. J Exp Med. 205:2235–2249. 2008. View Article : Google Scholar : PubMed/NCBI
18	Eue I, Pietz B, Storck J, Klempt M and Sorg C: Transendothelial migration of 27E10⁺ human monocytes. Int Immunol. 12:1593–1604. 2000. View Article : Google Scholar : PubMed/NCBI
19	Kerkhoff C, Hofmann HA, Vormoor J, et al: Binding of two nuclear complexes to a novel regulatory element within the human S100A9 promoter drives the S100A9 gene expression. J Biol Chem. 277:41879–41887. 2002. View Article : Google Scholar : PubMed/NCBI
20	Melkonyan H, Hofmann HA, Nacken W, Sorg C and Klempt M: The gene encoding the myeloid-related protein 14 (MRP14), a calcium-binding protein expressed in granulocytes and monocytes, contains a potent enhancer element in the first intron. J Biol Chem. 273:27026–27032. 1998. View Article : Google Scholar
21	Pi J, Qu W, Reece JM, Kumagai Y and Waalkes MP: Transcription factor Nrf2 activation by inorganic arsenic in cultured keratinocytes: involvement of hydrogen peroxide. Exp Cell Res. 290:234–245. 2003. View Article : Google Scholar : PubMed/NCBI
22	Wang XJ, Sun Z, Chen W, Li Y, Villeneuve NF and Zhang DD: Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1-C151: enhanced Keap1-Cul3 interaction. Toxicol Appl Pharmacol. 230:383–389. 2008. View Article : Google Scholar : PubMed/NCBI
23	Wang XJ, Sun Z, Chen W, Eblin KE, Gandolfi JA and Zhang DD: Nrf2 protects human bladder urothelial cells from arsenite and monomethylarsonous acid toxicity. Toxicol Appl Pharmacol. 225:206–213. 2007. View Article : Google Scholar : PubMed/NCBI
24	Lin L, Stringfield TM, Shi X and Chen Y: Arsenite induces a cell stress-response gene, RTP801, through reactive oxygen species and transcription factors Elk-1 and CCAAT/enhancer-binding protein. Biochem J. 392:93–102. 2005. View Article : Google Scholar : PubMed/NCBI
25	Barchowsky A, Dudek EJ, Treadwell MD and Wetterhahn KE: Arsenic induces oxidant stress and NF-kappa B activation in cultured aortic endothelial cells. Free Radic Biol Med. 21:783–790. 1996. View Article : Google Scholar : PubMed/NCBI
26	Barchowsky A, Roussel RR, Klei LR, et al: Low levels of arsenic trioxide stimulate proliferative signals in primary vascular cells without activating stress effector pathways. Toxicol Appl Pharmacol. 159:65–75. 1999. View Article : Google Scholar
27	Xu K, Yen T and Geczy CL: IL-10 upregulates macrophage expression of the S100 protein S100A8. J Immunol. 166:6358–6366. 2001. View Article : Google Scholar : PubMed/NCBI
28	Kuwayama A, Kuruto R, Horie N, Takeishi K and Nozawa R: Appearance of nuclear factors that interact with genes for myeloid calcium binding proteins (MRP-8 and MRP-14) in differentiated HL-60 cells. Blood. 81:3116–3121. 1993.PubMed/NCBI
29	Shen SC, Yang LY, Lin HY, Wu CY, Su TH and Chen YC: Reactive oxygen species-dependent HSP90 protein cleavage participates in arsenical As(+3)- and MMA(+3)-induced apoptosis through inhibition of telomerase activity via JNK activation. Toxicol Appl Pharmacol. 229:239–251. 2008.PubMed/NCBI
30	Smith KR, Klei LR and Barchowsky A: Arsenite stimulates plasma membrane NADPH oxidase in vascular endothelial cells. Am J Physiol Lung Cell Mol Physiol. 280:L442–L449. 2001.PubMed/NCBI
31	Benedyk M, Sopalla C, Nacken W, et al: HaCaT keratinocytes overexpressing the S100 proteins S100A8 and S100A9 show increased NADPH oxidase and NF-kappaB activities. J Invest Dermatol. 127:2001–2011. 2007. View Article : Google Scholar : PubMed/NCBI