Bisphenol A (BPA) has been known for many years as endocrine disrupting chemical. In recent years, awareness of its negative effects on health has increased, which has encouraged the tightening of regulations regarding its use. This is the reason for the development and use of BPA analogues, which are newer compounds with a similar chemical structure to BPA. Recent studies also attribute immunomodulatory properties to BPA, as well as to its analogue, which we verified in our master's thesis.
We studied the effect of nine BPA analogs on modulation of seven cytokines in three lymphoblastoid cell lines (LCL). First, we used the MTS cell viability assay to determine the effect of selected bisphenols on cell viability. For this purpose, we determined the half inhibitory concentration (IC50), at which 50 % of the cells were still metabolically active. The determined IC50 values differed significantly among the bisphenols. The lowest average IC50 value and thus the highest cytotoxicity for this type of cells was determined by the following analogues: BPP (IC50 = 27,9 μM), BPAF (IC50 = 52,6 μM), BPAP (IC50 =57,7 μM) and BPB (IC50 =97,7 μM). Lower cytotoxicity was determined for BPA (IC50 = 175,5 μM), while the other studied analogues (BPE, 2,4-BPS, BPF and TMBPF) had higher IC50 values that exceeded the highest tested concentration of 200 μM. We found that the IC50 value is inversely proportional to the logP value, which is directly related to lipophilicity. The correlation was high, so there is a strong correlation between lipophilicity and cytotoxicity.
Next, we determined the influence of selected BPA analogues on the modulation of seven cytokines. LCL cells were exposed to three different concentrations of selected bisphenols, 10 μM, 100 nM and 10 nM, activated with a combination of ionomycin and PMA, and then we evaluated the effect on release of cytokines by a flow cytometry. At 10 μM bisphenols caused a decrease in most of the measured cytokines, specifically the pro-inflammatory cytokines IL-2, IL-6 and TNF-α as well as the immuno-regulatory cytokine IL-10, which indicate their immunosuppressive effects at high concentrations. At the physiologically possible concentrations of 100 nM and 10 nM, bisphenols had a pro-inflammatory effect, as they increased the concentration of the pro-inflammatory cytokine IL-2 and the pleiotropic IFN-γ and decreased the concentration of the immuno-regulatory cytokine IL-10. Results indicate that the immunomodulatory effects of BPA and its analogues on cytokine production are not concentration-dependent, which is also in line with previous studies.
From the results of this Master's Thesis, we can conclude that BPA analogues have an immunomodulatory effect and otherwise affect the secretion of cytokines in LCL cells. Additional studies examining the impact of BPA analogs on immune system modulation would be worthwhile.
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