Bisphenol A suppresses Th1-type immune response in human peripheral blood mononuclear cells in vitro

Abstract

Bisphenol A (BPA) is a widely used plasticizer, which came into focus because of its genotoxic and sensitizing potential. Besides its toxic properties, BPA is also well-known for its antioxidant chemical properties. This in vitro study investigated the interference of BPA with interferon-γ (IFN-γ)-induced tryptophan breakdown and neopterin production in human peripheral blood mononuclear cells (PBMC). The pro-inflammatory cytokine IFN-γ induces the conversion of the essential amino acid tryptophan into kynurenine via the enzyme indoleamine-2,3-dioxygenase (IDO-1). In parallel, GTP-cyclohydrolase produces neopterin, a marker of immune activation. A model system of phytohaemagglutinin (PHA)-stimulated PBMC was used to assess potential immunomodulatory properties of BPA. Treatment of cells with BPA [12.5-200μM] resulted in a significant and dose-dependent suppression of mitogen-induced tryptophan breakdown and neopterin formation along with a decrease of IFN-γ levels. Similar but less pronounced effects were observed in unstimulated cells. We postulate that the inhibitory effects of BPA on both T-cell activation and IDO-1 activity that we describe here may be critical for immune surveillance and is likely to influence T helper (Th) type 1/Th2 balance. Such immunosuppressive effects likely contribute to counteract inflammation. Further studies are required to address the in vivo relevance our in vitro findings.

The Influence of Bisphenol a on the Nitrergic Nervous Structures in the Domestic Porcine Uterus

“…However, all neuronal substances included in the present study are involved in pro- or anti-inflammatory reactions. Strong anti-inflammatory activity is characteristic for VIP and PACAP, which inhibit the synthesis of pro-inflammatory factors [ 56 ], while SP is known as a substance showing pro-inflammatory activity affecting the lymphocytes and macrophages and causing an increase in the level of TNF-α [ 57 ]. In turn, the participation of NO in inflammatory processes is not quite clear.…”

Human Peripheral Blood Mononuclear Cell Function and Dendritic Cell Differentiation Are Affected by Bisphenol-A Exposure

“…These results are in agreement with those observed in murine immune system cells, where it has been described that the exposure to high doses (20μM) of BPA increases the proliferation of concanavalin A-stimulated splenocytes [ 36 ] and of thymocytes [ 37 ], while analogous results were found also in goldfish [ 38 ]. By contrast Gostner et al [ 55 ] found a decreased cell viability in human PBMCs treated with micromolar doses of BPA, as well as other studies [ 54 ] reporting an immune-suppression activity of high doses of the chemical in lupus-prone murine models, thus confirming a broad, non-monotonic, BPA effects on immune cells.…”

“…BPA, as endocrine disruptor with natural estrogen activity, at small doses can cause different effects from those generated at higher doses, with an oscillating non-monotonic dose response. Numerous evidences, however, have shown that BPA can have significant metabolic and immune effects at environmental low doses, which may not be apparent at higher doses used in traditional toxicological studies [ 13 , 54 , 55 ]. For example, at micromolar doses, the toxic effect on immune cells could regulate expression of a distinct set of genes involved in growth and development, different from those regulated at low doses [ 13 , 54 , 55 ].…”

“…Numerous evidences, however, have shown that BPA can have significant metabolic and immune effects at environmental low doses, which may not be apparent at higher doses used in traditional toxicological studies [ 13 , 54 , 55 ]. For example, at micromolar doses, the toxic effect on immune cells could regulate expression of a distinct set of genes involved in growth and development, different from those regulated at low doses [ 13 , 54 , 55 ]. In particular, Gostner et al [ 55 ] reported an inhibitory effect of BPA on T-cell proliferation, with immunosuppressive effects.…”

“…For example, at micromolar doses, the toxic effect on immune cells could regulate expression of a distinct set of genes involved in growth and development, different from those regulated at low doses [ 13 , 54 , 55 ]. In particular, Gostner et al [ 55 ] reported an inhibitory effect of BPA on T-cell proliferation, with immunosuppressive effects. The BPA concentrations applied in this study (0.1 and 1nM) are widely considered as “low-dose” used for in vitro experiments and are consistent with human chronic exposure [ 11 , 13 , 56 , 57 ], with different effects on cell proliferation.…”