Abstract
The innate immune response, the first line of defense against invading pathogens, can be perturbed by environmental toxicants such as arsenic. This study reports the effects of arsenic on innate immunity of zebrafish. Respiratory burst activity, messenger RNA expression of tumor necrosis factor α (TNF-α), a primer of the respiratory burst response, and mRNA expression of the antiviral cytokines interferon (IFN) and Mx, before and after viral infection, were examined in arsenic-exposed zebrafish larvae. Respiratory burst activity and TNF-α expression were decreased upon arsenic exposure, indicating inhibition of TNF-α priming of the respiratory burst response. Arsenic enhanced IFN expression slightly over time, but reduced Mx expression. In zebrafish infected with snakehead rhabdovirus, arsenic decreased induction and altered the kinetics of IFN and Mx upon infection. Differences in IFN and Mx expression in arsenic-exposed larvae point toward an interruption of the Janus kinase–signal transducer and activator of transcription (JAK/STAT) pathway.
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References
Altmann SM, Mellon MT, Distel DL, Kim CH, (2003) Molecular and functional analysis of an interferon gene from the zebrafish, Danio rerioJ Virol 77: 1992–2002
Altmann SM, Mellon MT, Johnson MC, Paw BH, Trede NS, Zon LI, Kim CH, (2004) Cloning and characterization of an Mx gene and its corresponding promoter from the zebrafish, Danio rerioDev Comp Immunol 28: 295–306
Beaman JR, Finch R, Gardner H, Hoffmann F, Rosencrance A, Zelikoff JT, (1999) Mammalian immunoassays for predicting the toxicity of malathion in a laboratory fish modelJ Toxicol Environ Health A 56: 523–542
Berg I, Schluter T, Gercken G, (1993) Increase of bovine alveolar macrophage superoxide anion and hydrogen peroxide release by dusts of different originJ Toxicol Environ Health 39: 341–354
Bernstam L, Nriagu J, (2000) Molecular aspects of arsenic stressJ Toxicol Environ Health B Crit Rev 3: 293–322
Bishayi B, Sengupta M, (2003) Intracellular survival of Staphylococcus aureus due to alteration of cellular activity in arsenic and lead intoxicated mature Swiss albino miceToxicology 184: 31–39
Bosnir J, Puntaric D, Skes I, Klaric M, Simic S, Zoric I, Galic R, (2003) Toxic metals in freshwater fish from the Zagreb area as indicators of environmental pollutionColl Antropol 27(Suppl 1): 31–39
Cavigelli M, Li WW, Lin A, Su B, Yoshioka K, Karin M, (1996) The tumor promoter arsenite stimulates AP-1 activity by inhibiting a JNK phosphataseEMBO J 15: 6269–6279
Chen NY, Ma WY, Huang C, Ding M, Dong Z, (2000) Activation of PKC is required for arsenite-induced signal transductionJ Environ Pathol Toxicol Oncol 19: 297–305
Chen YC, Lin-Shiau SY, Lin JK (1998) Involvement of reactive oxygen species and caspase 3 activation in arsenite-induced apoptosisJ Cell Physiol 177: 324–333
Cheng HY, Li P, David M, Smithgall TE, Feng L, Lieberman MW, (2004) Arsenic inhibition of the JAK-STAT pathwayOncogene 23: 3603–3612
Ciapetti G, Granchi D, Verri E, Savarino L, Cenni E, Savioli F, Pizzoferrato A, (1998) Fluorescent microplate assay for respiratory burst of PMNs challenged in vitro with orthopedic metalsJ Biomed Mater Res 41: 455–460
Corsini E, Asti L, Viviani B, Marinovich M, Galli CL, (1999) Sodium arsenate induces overproduction of interleukin-1 alpha in murine keratinocytes: role of mitochondriaJ Invest Dermatol 113: 760–765
Dewas C, Dang PM, Gougerot-Pocidalo MA, El-Benna J, (2003) TNF-alpha induces phosphorylation of p47(phox) in human neutrophils: partial phosphorylation of p47phox is a common event of priming of human neutrophils by TNF-alpha and granulocyte-macrophage colony-stimulating factor. J Immunol 171: 4392–4398
Elsasser MS, Roberson BS, Hetrick FM, (1986) Effects of metals on the chemiluminescent response of rainbow trout (Salmo gairdneri) phagocytesVet Immunol Immunopathol 12: 243–250
Germolec DR, Yoshida T, Gaido K, Wilmer JL, Simeonova PP, Kayama F, Burleson F, Dong W, Lange RW, Luster MI, (1996) Arsenic induces overexpression of growth factors in human keratinocytesToxicol Appl Pharmacol 141: 308–318
Goytia-Acevedo RC, Cebrian ME, Calderon-Aranda ES, (2003) Differential effects of arsenic on intracellular free calcium levels and the proliferative response of murine mitogen-stimulated lymphocytesToxicology 189: 235–244
Green SP, Hamilton JA, Uhlinger DJ, Phillips WA, (1994) Expression of p47-phox and p67-phox proteins in murine bone marrow-derived macrophages: enhancement by lipopolysaccharide and tumor necrosis factor alpha but not colony stimulating factor 1J Leukoc Biol 55: 530–535
Gulyas H, Labedzka M, Gercken G, (1990) Depression of alveolar macrophage hydrogen peroxide and superoxide anion release by mineral dusts: correlation with antimony, lead, and arsenic contentsEnviron Res 51: 218–229
Hermann AC, Millard PJ, Blake SL, Kim CH, (2004) Development of a respiratory burst assay using zebrafish kidneys and embryosJ Immunol Methods 292: 119–129
Hermesz E, Gazdag AP, Ali KS, Nemcsok J, Abraham M, (2002) Differential regulation of the two metallothionein genes in common carpActa Biol Hung 53: 343–350
Huang C, Ke Q, Costa M, Shi X, (2004) Molecular mechanisms of arsenic carcinogenesisMol Cell Biochem 255: 57–66
Jacobson SV, Trucksis M, Kane AS, Reimschuessel R, (1999) Superoxide production in phagocytes obtained from Mycobacterium marinum-stimulated goldfish (Carassius auratus) that were exposed to copperAm J Vet Res 60: 669–675
Jault C, Pichon L, Chluba J, (2004) Toll-like receptor gene family and TIR-domain adapters in Danio rerioMol Immunol 40: 759–771
Jiang G, Bi K, Tang T, Zhang Y, Ren H, Jiang F, Ren Q, Zhen G, Liu C, Peng J, Quo G, Liu X, Tian Z, (2003) Effect of arsenic trioxide on cytokine expression by acute promyelocytic leukemia cellsChin Med J 116: 1639–1643
Koropatnick J, Zalups RK, (1997) Effect of non-toxic mercury, zinc or cadmium pretreatment on the capacity of human monocytes to undergo lipopolysaccharide-induced activationBr J Pharmacol 120: 797–806
Kothary RK, Candido EP, (1982) Induction of a novel set of polypeptides by heat shock or sodium arsenite in cultured cells of rainbow trout, Salmo gairdnerii. Can J Biochem 60: 347–355
Lantz RC, Parliman G, Chen GJ, Barber D, Winski S, Carter DE, (1995) Effect of arsenic exposure on alveolar macrophage function, II: effect of slightly soluble forms of As(III) and As(V)Environ Res 68:59–67
Lemaire-Gony S, Mayer-Gostan N, (1994) In vitro dose-response study of the effect of cadmium on eel (Anguilla anguilla) gill Na+/K+-ATPase activitiesEcotoxicol Environ Saf 28: 43–52
Matsumoto M, Kikkawa S, Kohase M, Miyake K, Seya T, (2002) Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signalingBiochem Biophys Res Commun 293: 1364–1369
Meijer AH, Gabby Krens SF, Medina Rodriguez IA, He S, Bitter W, Ewa Snaar-Jagalska B, Spaink HP, (2004) Expression analysis of the Toll-like receptor and TIR domain adaptor families of zebrafish. Mol Immunol 40: 773–783
Niwa Y, Ozaki Y, Kanoh T, Akamatsu H, Kurisaka M, (1996) Role of cytokines, tyrosine kinase, and protein kinase C on production of superoxide and induction of scavenging enzymes in human leukocytes. Clin Immunol Immunopathol 79: 303–313
Phelan PE, Pressley ME, Witten PE, Mellon MT, Blake SL, Kim CH (2004) Characterization of snakehead rhabdovirus infection of zebrafish. (Danio rerio). J Virol 79, 1842–1852
Phillips WA, Croatto M, Hamilton JA, (1992) Priming of the respiratory burst of bone marrow-derived macrophages is associated with an increase in protein kinase C contentJ Immunol 149: 1016–1022
Rodgers K, Xiong S, (1997) Contributions of inflammatory mast cell mediators to alterations in macrophage function after malathion administrationInt J Immunopharmacol 19: 149–156
Roussel RR, Barchowsky A, (2000) Arsenic inhibits NF-kappaB-mediated gene transcription by blocking IkappaB kinase activity and IkappaBalpha phosphorylation and degradationArch Biochem Biophys 377: 204–212
Sato S, Sugiyama M, Yamamoto M, Watanabe Y, Kawai T, Takeda K, Akira S, (2003) Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIP) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signalingJ Immunol 171: 4304–4310
Schulz H, Nagymajtenyi L, Institoris L, Papp A, Siroki O, (2002) A study on behavioral, neurotoxicological, and immunotoxicological effects of subchronic arsenic treatment in ratsJ Toxicol Environ Health A 65: 1181–1193
Sengupta M, Bishayi B, (2002) Effect of lead and arsenic on murine macrophage responseDrug Chem Toxicol 25: 459–472
Thelen M, Rosen A, Nairn AC, Aderem A, (1990) Tumor necrosis factor alpha modifies agonist-dependent responses in human neutrophils by inducing the synthesis and myristoylation of a specific protein kinase C substrateProc Natl Acad Sci U S A 87: 5603–5607
Tisler T, Zagorc-Koncan J, (2002) Acute and chronic toxicity of arsenic to some aquatic organismsBull Environ Contam Toxicol 69: 421–429
Voie OA, Wiik P, Fonnum F, (1998) Ortho-substituted polychlorinated biphenyls activate respiratory burst measured as luminol-amplified chemoluminescence in human granulocytesToxicol Appl Pharmacol 150: 369–375
Wang YC, Chaung RH, Tung LC, (2004) Comparison of the cytotoxicity induced by different exposure to sodium arsenite in two fish cell linesAquat Toxicol 69: 67–79
Ward RA, Nakamura M, McLeish KR, (2000) Priming of the neutrophil respiratory burst involves p38 mitogen-activated protein kinase-dependent exocytosis of flavocytochrome b558-containing granulesJ Biol Chem 275: 36713–36719
Wijeweera JB, Gandolfi AJ, Parrish A, Lantz RC,(2001) Sodium arsenite enhances AP-1 and NFkappaB DNA binding and induces stress protein expression in precision-cut rat lung slicesToxicol Sci 61:283–294
Yamamoto M, Sato S, Mori K, Hoshino K, Takeuchi O, Takeda K, Akira S, (2002) Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signalingJ Immunol 169:6668–6672
Yang C, Frenkel K, (2002) Arsenic-mediated cellular signal transduction, transcription factor activation, and aberrant gene expression: implications in carcinogenesis J Environ Pathol Toxicol Oncol 21: 331–342
Yatsuyanagi J, Ogiso T, (1988) Zinc inhibition of respiratory burst in zymosan-stimulated neutrophils: a possible membrane action of zinc. Chem Pharm Bull (Tokyo) 36: 1035–1040
Yen HT, Chiang LC, Wen KH, Chang SF, Tsai CC, Yu CL, Yu HS, (1996) Arsenic induces interleukin-8 expression in cultured keratinocytes. Arch Dermatol Res 288: 716–717
Acknowledgments
The authors thank Akshata Nayak for technical assistance and Dr. William Halteman for advice on statistical procedures. We also thank Adria Elskus, Paul Millard, and Mary Rumpho for scientific and editorial advice on the manuscript.
This study was supported by funds administrated through the Maine Agricultural and Forest Experiment Station. This is Maine Agricultural and Forest Experiment Station publication 2748.
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Hermann, A.C., Kim, C.H. Effects of Arsenic on Zebrafish Innate Immune System. Mar Biotechnol 7, 494–505 (2005). https://doi.org/10.1007/s10126-004-4109-7
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DOI: https://doi.org/10.1007/s10126-004-4109-7