Abstract
Purpose
The aim of this study is to determine whether exposure to hazardous chemicals alters chemokine or cytokine production in macrophages and link these events to changes in intracellular signaling pathways and activation of specific gene promoters.
Methods
RAW 264.7 mouse macrophages were treated with selected toxic industrial chemicals (TICs) and examined for changes in immune function. Luminex multiplex technology was used to assess changes in cytokine/chemokine expression and activation of kinase signaling pathways. In addition, a panel of macrophage cell lines with promoter-specific luciferase reporter genes were generated and treated with the TICs, and transcriptional responses to these chemicals were detected by changes in luminescence.
Results
Changes in expression of cytokines and chemokines were linked to changes in the activation state of intracellular signaling pathways. Overall, the findings reveal that sublytic levels of TICs can alter the profile of cytokines and chemokines expressed by macrophages, with a pattern that suggests immunosuppression. The data demonstrate that critical changes in immune function correlate with activation of kinase signaling pathways in macrophages.
Conclusions
These data provide insight into the effects of sublytic doses of selected TICs on macrophage function, with a particular emphasis on identifying changes in expression of cytokines and chemokines. These altered patterns in immune function were linked to changes in the activation state of intracellular signaling pathways. The data strongly suggest that small amounts of TICs can have subtle, yet very critical, effects on macrophages.
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References
Akbar M, Brewer JM, Grant MH (2011) Effect of chromium and cobalt ions on primary human lymphocytes in vitro. J Immunotoxicol 8(2):140–149. doi:10.3109/1547691X.2011.553845
Casillas AM, Hiura T, Li N, Nel AE (1999) Enhancement of allergic inflammation by diesel exhaust particles: permissive role of reactive oxygen species. Ann Allergy Asthma Immunol 83(6 Pt 2):624–629. doi:10.1016/S1081-1206(10)62884-0
Dale DC, Boxer L, Liles WC (2008) The phagocytes: neutrophils and monocytes. Blood 112(4):935–945. doi:10.1182/blood-2007-12-077917
DeLeo FR (2004) Modulation of phagocyte apoptosis by bacterial pathogens. Apoptosis 9:399–413. doi:10.1023/B:APPT.0000031448.64969.fa
Fair PA, Driscoll E, Mollenhauer MA, Bradshaw SG, Yun SH, Kannan K, Bossart GD, Keil DE, Peden-Adams MM (2011) Effects of environmentally-relevant levels of perfluorooctane sulfonate on clinical parameters and immunological functions in B6C3F1 mice. J Immunotoxicol 8(1):17–29. doi:10.3109/1547691X.2010.527868
Fukuyama T, Tajima Y, Ueda H, Hayashi K, Shutoh Y, Harada T, Kosaka T (2010) Apoptosis in immunocytes induced by several types of pesticides. J Immunotoxicol 7(1):39–56. doi:10.3109/15476910903321704
Hiura TS, Kaszubowski MP, Li N, Nel AE (1999) Chemicals in diesel exhaust particles generate reactive oxygen radicals and induce apoptosis in macrophages. J Immunol 163(10):5582–5591
Loose LD, Pittman KA, Benitz KF, Silkworth JB, Mueller W, Coulston F (1978) Environmental chemical-induced immune dysfunction. Ecotoxicol Environ Saf 2(2):173–198
Ng D, Kokot N, Hiura T, Faris M, Saxon A, Nel A (1998) Macrophage activation by polycyclic aromatic hydrocarbons: evidence for the involvement of stress-activated protein kinases, activator protein-1, and antioxidant response elements. J Immunol 161(2):942–951
Osterburg AR, Robinson CT, Schwemberger S, Mokashi V, Stockelman M, Babcock GF (2010) Sodium tungstate (Na2WO4) exposure increases apoptosis in human peripheral blood lymphocytes. J Immunotoxicol 7(3):174–182. doi:10.3109/15476911003631617
Riahi B, Rafatpanah H, Mahmoudi M, Memar B, Fakhr A, Tabasi N, Karimi G (2011) Evaluation of suppressive effects of paraquat on innate immunity in Balb/c mice. J Immunotoxicol 8(1):39–45. doi:10.3109/1547691X.2010.543095
Smith DC, Smith MJ, White KL (2010) Systemic immunosuppression following a single pharyngeal aspiration of 1,2:5,6-dibenzanthracene in female B6C3F1 mice. J Immunotoxicol 7(3):219–231. doi:10.3109/1547691X.2010.487193
Udoji F, Martin T, Etherton R, Whalen MM (2010) Immunosuppressive effects of triclosan, nonylphenol, and DDT on human natural killer cells in vitro. J Immunotoxicol 7(3):205–212. doi:10.3109/15476911003667470
Vos JG (1977) Immune suppression as related to toxicology. CRC Crit Rev Toxicol 5(1):67–101. doi:10.3109/10408447709101342
Wang S, Prophete C, Soukup JM, Chen LC, Costa M, Ghio A, Qu Q, Cohen MD, Chen H (2010) Roles of MAPK pathway activation during cytokine induction in BEAS-2B cells exposed to fine World Trade Center (WTC) dust. J Immunotoxicol 7(4):298–307. doi:10.3109/1547691X.2010.509289
Zheng L, Dong GH, Zhang YH, Liang ZF, Jin YH, He QC (2011) Type 1 and Type 2 cytokines imbalance in adult male C57BL/6 mice following a 7-day oral exposure to perfluorooctanesulfonate (PFOS). J Immunotoxicol 8(1):30–38. doi:10.3109/1547691X.2010.537287
Acknowledgments
The methodology is based on research sponsored by the U.S. Defense Threat Reduction Agency and the Air Force Research Laboratory under Research Grant HDTRA1-07-1-0027 (PI: Ballard) and the Air Force Research Laboratory under Cooperative Agreement FA8650-05-2-6523 (PI: Regens). This paper is an independent product and does not necessarily represent the official views or policies of the sponsoring agencies or the U.S. Government.
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Barua, S., Larabee, J., Regens, J.L. et al. Differential inflammatory responses triggered by toxic small molecules. Environ Sci Pollut Res 19, 619–627 (2012). https://doi.org/10.1007/s11356-011-0593-2
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DOI: https://doi.org/10.1007/s11356-011-0593-2