Non-coplanar polychlorinated biphenyl (PCB)-induced immunotoxicity is coincident with alterations in the serotonergic system

Duffy-Whritenour, Jessica E.; Kurtzman, Rebecca Z.; Kennedy, Sarah M.; Zelikoff, Judith T.

doi:10.3109/1547691x.2010.512277

Cited by 19 publications

(12 citation statements)

References 32 publications

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“…The reduction in formation/release of IL-2, a chief cytokine responsible for differentiation and maturation of T-cells, would also be in agreement with the reduction in T-cell functionality previously noted by Hulme et al (2012). Moreover, previous research has shown the ability of PCBs to suppress IL-2 formation/secretion by Steppan et al (1993), as well as reducing adaptive immune responses specific to, T-cells (Lu & Wu 1985;Tryphonas 1995;Tan et al 2003;Duffy-Whritenour et al 2010).…”

Section: Discussionsupporting

confidence: 81%

“…Considering recent reviews by Taylor et al (2013), Tang et al (2014), and Bodin et al (2015) pointing at the substantial knowledge gained about the role of PCBs in Type 2 diabetes, and speculating (in the absence of experimental evidence) about a positive association between PCBs and T1D, this study sheds a light on PCB-153 action in the context of experimental T1D. Whereas PCB-153 levels in sera of treated mice were not identified here, the doses and route of exposure were comparable to those used in previous animal studies (Smialowicz et al 1997;Ropstad et al 2006;Strathmann et al 2006;Duffy-Whritenour et al 2010). The subchronic low-dose exposure used here fell within the range reported to provide PCB-153 levels (NTP 2006) comparable to PCB-153 levels observed in epidemiology studies (Glynn et al 2008;Leijs et al 2009).…”

Section: Discussionsupporting

confidence: 61%

“…Measures of glycemia levels and body weights were performed weekly. Doses and route of PCB-153 exposure were chosen based on previous studies (Smialowicz et al 1997;Ropstad et al 2006;Strathmann et al 2006;Duffy-Whritenour et al 2010), and a potential for low-dose subchronic exposures to generate pollutant levels (NTP 2006) similar to those observed in various epidemiologic studies (Glynn et al 2008;Leijs et al 2009). …”

Section: Diabetes Incidence Studiesmentioning

confidence: 99%

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Exposure to polychlorinated biphenyl-153 decreases incidence of autoimmune Type 1 diabetes in non-obese diabetic mice

Kuiper

Moran

Ćetković-Cvrlje

2016

Journal of Immunotoxicology

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Type 1 diabetes (T1D) incidence has been steadily rising across the globe. Exposure to persistent organic pollutants (POP) has been implied as one potential cause of increased T1D occurrence. Since data regarding the role of POP polychlorinated biphenyl-153 (PCB-153) in autoimmune T1D development in experimental animal models are lacking, this study sought to evaluate the effect of PCB-153 exposure on T1D development in a non-obese diabetic (NOD) mouse model. As T1D is an autoimmune, T-cell-dependent disease, PCB-153 effects on T-cells were studied as well. Pre-diabetic 8-9-week-old NOD mice were exposed to intraperitoneal injections of PCB-153 in a 10-day short- (subacute exposure; 0.5 or 50 mg/kg) or 16-week long-term (subchronic exposure; 0.125 or 12.5 mg/kg) fashion. A significant decrease in incidence of T1D was observed in both low- and high-dose subchronically exposed mice. Analysis of various immune parameters, including T-cell types and subtypes, T-cell proliferative responses - as well as their cytokine secretions, revealed that both short- and long-term exposure to PCB-153 caused significant immunosuppression. PCB-153-induced immunosuppression was reflected in reductions in levels of T helper (T)-type cells and their functions after subacute treatment with low- and high-dose PCB-153. In agreement, decreased levels of T cells, reduced proliferation and IL-2 secretion seemed to be a mechanism of PCB-153 action in the development of T1D in subchronically exposed mice. In conclusion, this study for the first time revealed the effects of PCB-153 on development of T1D, bridging the existing experimental knowledge gap regarding the association of non-dioxin-like PCBs and T1D.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 61%

Section: Diabetes Incidence Studiesmentioning

confidence: 99%

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Exposure to polychlorinated biphenyl-153 decreases incidence of autoimmune Type 1 diabetes in non-obese diabetic mice

Kuiper

Moran

Ćetković-Cvrlje

2016

Journal of Immunotoxicology

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“…A large 2-year exposure study with female SD rats found effects on thyroid and thyroid hormone levels, liver hypertrophy, fatty changes, cholangiomas, and other changes, as well as inflammation of uterus and ovary (NTP, 2006). Occupational exposure to PCB 153, for example among farmers and industrial workers, has also been associated with increased incidence of immunotoxicity (Ritchie et al , 2003; Duffy-Whritenour et al , 2010). Molecular mechanisms involved in these adverse biological effects are not completely understood.…”

Section: Discussionmentioning

confidence: 99%

PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)

Senthilkumar

Robertson

Ludewig

2012

Toxicology and Applied Pharmacology

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Polychlorinated Biphenyls (PCBs), ubiquitous environmental pollutants, are characterized by long term-persistence in the environment, bioaccumulation, and biomagnification in the food chain. Exposure to PCBs may cause various diseases, affecting many cellular processes. Deregulation of the telomerase and the telomere complex leads to several biological disorders. We investigated the hypothesis that PCB153 modulates telomerase activity, telomeres and reactive oxygen species resulting in the deregulation of cell growth. Exponentially growing immortal human skin keratinocytes (HaCaT) and normal human foreskin keratinocytes (NFK) were incubated with PCB153 for 48 and 24 days, respectively, and telomerase activity, telomere length, superoxide level, cell growth, and cell cycle distribution were determined. In HaCaT cells exposure to PCB153 significantly reduced telomerase activity, telomere length, cell growth and increased intracellular superoxide levels from day 6 to day 48, suggesting that superoxide may be one of the factors regulating telomerase activity, telomere length and cell growth compared to untreated control cells. Results with NFK cells showed no shortening of telomere length but reduced cell growth and increased superoxide levels in PCB153-treated cells compared to untreated controls. As expected, basal levels of telomerase activity were almost undetectable, which made a quantitative comparison of treated and control groups impossible. The significant down regulation of telomerase activity and reduction of telomere length by PCB153 in HaCaT cells suggest that any cell type with significant telomerase activity, like stem cells, may be at risk of premature telomere shortening with potential adverse health effects for the affected organism.

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“…Several indirect mechanisms have been proposed, such as signaling via the neural-immune axis, perhaps by affecting calcium homeostasis or serotonergic systems (Duffy-Whritenour et al 2010; Pessah et al 2010). …”

Section: Pcbs Nhl and The Immune Systemmentioning

confidence: 99%

Current Status of the Epidemiologic Evidence Linking Polychlorinated Biphenyls and Non-Hodgkin Lymphoma, and the Role of Immune Dysregulation

Kramer¹,

Hikel²,

Adams³

et al. 2012

Environ Health Perspect

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Background: Although case–control studies conducted to date have largely affirmed the relationship between polychlorinated biphenyls (PCBs) and non-Hodgkin lymphoma (NHL), occupational cohort studies of PCB-exposed workers have been generally interpreted as negative, thereby raising doubts about a potential causal association. A common theme of immune dysregulation unifies many of NHL’s strongest risk factors, and several authors have posited that subclinical immune dysregulation may increase NHL risk by decreasing host resistance, reducing control of cellular proliferation and differentiation, and diminishing tumor surveillance mechanisms.Objectives: The goals of this review were a) to evaluate the epidemiological research examining the association between PCB exposure and NHL and discuss the contribution to the weight of evidence of case–control studies and occupational cohort studies; and b) to summarize the evidence for immune dysregulation as a means by which PCBs may cause NHL.Methods: We performed a literature search using PubMed and seven additional online biomedical and toxicological referencing libraries to identify literature published through August 2011.Discussion and Conclusions: Overall, we conclude that the weight of evidence supports a causal role of PCBs in lymphomagenesis. The strongest epidemiological evidence for the relationship between PCBs and NHL comes from case–control studies conducted among the general population. Epidemiological and toxicological data demonstrating immunosuppressive and inflammatory effects of PCBs further contribute to the weight of evidence by providing a plausible explanation for how PCBs can cause NHL through immune dysregulation.

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Non-coplanar polychlorinated biphenyl (PCB)-induced immunotoxicity is coincident with alterations in the serotonergic system

Cited by 19 publications

References 32 publications

Exposure to polychlorinated biphenyl-153 decreases incidence of autoimmune Type 1 diabetes in non-obese diabetic mice

Exposure to polychlorinated biphenyl-153 decreases incidence of autoimmune Type 1 diabetes in non-obese diabetic mice

PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)

Current Status of the Epidemiologic Evidence Linking Polychlorinated Biphenyls and Non-Hodgkin Lymphoma, and the Role of Immune Dysregulation

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