Exposure to polychlorinated biphenyl-153 decreases incidence of autoimmune Type 1 diabetes in non-obese diabetic mice.
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 (TH)-type cells and their functions after subacute treatment with low- and high-dose PCB-153. In agreement, decreased levels of THcells, 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.
a Department of Biological Sciences , St. Cloud State University , St. Cloud , MN , USA.|b Laboratory for Immunology , St. Cloud State University , St. Cloud , MN , USA.
Jordan
J
Kuiper
a Department of Biological Sciences , St. Cloud State University , St. Cloud , MN , USA.
Michelle
M
Moran
a Department of Biological Sciences , St. Cloud State University , St. Cloud , MN , USA.|b Laboratory for Immunology , St. Cloud State University , St. Cloud , MN , USA.
Marina
M
Cetkovic-Cvrlje
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000276:immunology*; D004785:Environmental Pollutants / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007165:Immunosuppression Therapy; D015994:Incidence; D051379:Mice; D016688:Mice, Inbred NOD; D023421:Models, Animal; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage* / Q000009:adverse effects; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D016207:Cytokines; D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl
Diabetes; PCB-153; T-cells; Type 1 diabetes; non-obese diabetic mice; persistent organic pollutants