Abstract
Objective
Tributyltin (TBT) compounds have been widely used as antifouling agents for shipbottom paint. The immune system is a target of TBT intoxication. We evaluated the effects of TBT chloride in macrophages, which have critical roles in the immune system, using a murine macrophage lineage cell line, J774.1,in vitro.
Methods
We examined tumor necrosis factor α (TNFα), interleukin-1β (IL-1β) andc-jun mRNA expression in J774.1 cells. The effects of TBT on the apoptosis of J774.1 cells were examined by determining the percentage of TUNEL-positive cells and caspase-3 activity.
Results
The mean values of the viabilities of J774.1 cells exposed to TBT decreased dose-dependently. The relative mRNA expression of TNFα increased dose-dependently, however, that of IL-1β was not significantly different among the groups. The mean percentage of TUNEL-positive cells increased dose-dependently. Increases in the caspase-3 activities of J774.1 cells were observed in the groups exposed to higher concentrations of TBT. The mean value of relative mRNA expression of c-Jun transcription factor increased dose-dependently.
Conclusions
The increases in the percentage of TUNEL-positive cells and in caspase-3 activity suggested that exposure to TBT induces apoptosis of J774.1 cells. The increases in the mRNA expression of TNFα andc-jun by TBT may be related to apoptosis in macrophages.
Similar content being viewed by others
References
Fent K. Ecotoxicology of organotin compounds. Crit. Rev. Toxicol. 1996;26:1–117.
Boyer IJ. Toxicity of dibutyltin, tributyltin and other organotin compounds to humans and to experimental animals. Toxicology 1989;55:253–298.
Horiguchi T. Organotin compounds and anomalies of genital organ in sea snail. Kagaku. 1998;68:546–551 (in Japanese).
Shim WJ, Oh JR, Kahng SH, Shim JH, Lee SH. Accumulation of tributyl- and triphenyltin compounds in Pacific oyster,Crassostrea gigas, from the Chinhae Bay System, Korea. Arch. Environ. Contam. Toxicol. 1998;35:41–47.
Ministry of the Environment. Discussion of Details. In: Ministry of the Environment, editor. Kankyo Hakusho, 2000. Tokyo; Gyousei, 2000;117–119 (in Japanese).
Strand J, Jacobsen JA, Pedersen B, Granmo A. Butyltin compounds in sediment and molluscs from the shipping strait between Denmark and Sweden. Environ. Pollut. 2003;124: 7–15.
Tsunoda M. Simultaneous determination of organotin compounds in fish and shellfish by gas chromatography with a flame photometric detector. Tohoku J. Exp. Med. 1993;169:167–178.
Nakano K, Saito K, Niimura M, Takahashi M, Takakura Y. Determination of tributyltin compounds in Fish, shellfishes and their processed products (II). Annu. Rep. Fukushima Inst. Public Health Environ. Sci. 1991;8:54–58 (in Japanese).
Short JW, Thrower FP. Accumulation of butyltins in muscle tissue of chinook salmon reared in sea pens treated with tri-n-butyltin. Mar. Pollut. Bull. 1986;17:542–545.
Whalen MM, Loganathan BG, Kannan K. Immunotoxicity of environmentally relevant concentrations of butyltins on human natural killer cellsin vitro. Environ. Res. 1999;81:108–116.
Kannan K, Falandysz J. Butyltin residues in sediments, fish, fish-eating birds, harbour porpoise and human tissues from the Polish coast of the Baltic Sea. Mar. Pollut. Bull. 1997;34:203–207.
Snoeij NJ, Penninks AH, Seinen W. Dibutyltin and tributyltin compounds induce thymus atrophy in rats due to a selective action on thymic lymphoblasts. Int. J. Immunopharmacol. 1988; 10:891–899.
Raffray M, Cohen GM. Thymocyte apoptosis as a mechanism for tributyltin-induced thymic atrophy in vivo. Arch. Toxicol. 1993;67:231–236.
Stridh H, Kimland M, Jones DP, Orrenius S, Hampton MB. Cytochrome c release and caspase activation in hydrogen peroxide- and tributyltin-induced apoptosis. FEBS Lett. 1998; 429:351–355.
Stridh H, Orrenius S, Hampton MB. Caspase involvement in the induction of apoptosis by the environmental toxicants tributyltin and triphenyltin. Toxicol. Appl. Pharmacol. 1999; 156:141–146.
Stridh H, Cotgreave I, Muller M, Orrenius S, Gigliotti D. Organotin-induced caspase activation and apoptosis in human peripheral blood lymphocytes. Chem. Res. Toxicol. 2001;14:791–798.
Aw TY, Nicotera P, Manzo L, Orrenius S. Tributyltin stimulates apoptosis in rat thymocytes. Arch. Biochem. Biophys. 1990;283:46–50.
Gennari A, Viviani B, Galli CL, Marinovich M, Pieters R, Corsini E. Organotins induce apoptosis by disturbance of [Ca2+]i and mitochondrial activity, causing oxidative stress and activation of caspases in rat thymocytes. Toxicol. Appl. Pharmacol. 2000;169:185–190.
Brenner DA, O’Hara M, Angel P, Chojkier M, Karin M. Prolonged activation ofjun and collagenase genes by tumor necrosis factor-α. Nature 1989;337:661–663.
Tsunoda M, Sharma RP. Modulation of tumor necrosis factor α expression in mouse brain after exposure to aluminum in drinking water. Arch. Toxicol. 1999;73:419–426.
Johnson VJ, Tsunoda M, Sharma RP. Increased production of proinflammatory cytokines by murine macrophages following oral exposure to sodium selenite but not to seleno-L-methionine. Arch. Environ. Contam. Toxicol. 2000;39:243–250.
Mathew JS, Sharma RP. Effect of all-trans-retinoic acid on cytokine production in a murine macrophage cell line. Int. J. Immunopharmacol. 2000;22:693–706.
Reiner SL, Zheng S, Corry DB, Locksley RM. Constructing polycompetitor cDNAs for quantitative PCR. J. Immunol. Methods 1993;165:37–46.
Benavides GR, Hubby B, Grosse WM, McGraw RA, Tarleton RL. Construction and use of a multi-competitor gene for quantitative RT-PCR using existing primer sets. J. Immunol. Methods 1995;181:145–156.
Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992;119:493–501.
Odaka C, Mizuochi T. Role of macrophage lysosomal enzymes in the degradation of nucleosomes of apoptotic cells. J. Immunol. 1999;163:5346–5352.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976;72:248–254.
Jayanthi S, McCoy MT, Ladenheim B, Cadet JL. Methamphetamine causes coordinate regulation of Src, Cas, Crk, and Jun N-terminal kinase-Jun pathway. Mol. Pharmacol. 2002; 61:1124–1131.
Mathison JC, Wolfson E, Ulevitch RJ. Participation of tumor necrosis factor in the mediation of gram negative bacteria lipopolysaccharide-induced injury in rabbits. J. Clin. Invest. 1988;81:1925–1937.
Kumar A, Commane M, Flickinger TW, Horvath CM, Stark GR. Detective TNF-α-induced apoptosis in STAT1-null cells due to low constitutive levels of caspases. Science 1997;278: 1630–1632.
Yu ZP, Matsuoka M, Wispriyono B, Iryo Y, Igisu H. Activation of mitogen-activated protein kinases by tributyltin in CCRF-CEM cells: Role of intracellular Ca2+ Toxicol. Appl. Pharmacol. 2000;168:200–207.
Corsini E, Terzoli A, Bruccoleri A, Marinovich M, Galli CL. Induction of tumor necrosis factor-αin vivo by a skin irritant, tributyltin, through activation of transcription factors: its pharmacological modulation by anti-inflammatory drugs. J. Invest. Dermatol. 1997;108:892–896.
Wilson MR. Apoptotic signal transduction: emerging pathways. Biochem. Cell. Biol. 1998;76:573–582.
Lavastre V, Girard D. Tributyltin induces human neutrophil apoptosis and selective degradation of cytoskeletal proteins by caspases. J. Toxicol. Environ. Health A 2002;65:1013–1024.
Zucker RM, Elstein KH, Thomas DJ, Rogers JM. Tributyltin and dexamethasone induce apoptosis in rat thymocytes by mutually antagonistic mechanisms. Toxicol. Appl. Pharmacol. 1994;127:163–170.
Dunn C, Wiltshire C, MacLaren A, Gillespie DAF. Molecular mechanism and biological functions of c-Jun N-terminal kinase signalling via the c-Jun transcription factor. Cell Signal. 2002;14:585–593.
Bossy-Wetzel E, Bakiri L, Yaniv M. Induction of apoptosis by the transcription factor c-Jun. EMBO J. 1997;16:1695–1709.
Zhou T, Zhou G, Song W, Eguchi N, Lu W, Lundin E, Jin T, Nordberg G. Cadmium-induced apoptosis and changes in expression ofp53, c-jun andMT-1 genes in testes and ventral prostate of rats. Toxicology, 1999;142:1–13.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nakano, K., Tsunoda, M. & Konno, N. Tributyltin (TBT) increases TNFα mRNA expression and induces apoptosis in the murine macrophage cell line in vitro. Environ Health Prev Med 9, 266–271 (2004). https://doi.org/10.1007/BF02898141
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02898141