Effects of four Fusarium toxins (fumonisin B(1), alpha-zearalenol, nivalenol and deoxynivalenol) on porcine whole-blood cellular proliferation.

The in vitro effects of four Fusarium toxins, fumonisin B1 (FB1), a-zearalenol (a-ZEA), nivalenol (NIV) and deoxynivalenol (DON), on mitogen-induced cell proliferation were determined in swine whole-blood cultures. Considering the lack of sufficient toxicological data both on single and in combination effects, in vitro studies may contribute to risk assessment of these toxins. Incubation with increasing concentrations of FB1 did not produce any consequence on proliferation; in contrast a-ZEA, NIV and DON showed an inhibitory effect. Dose–response curves for each mycotoxin were generated. NIV was found to be the most potent toxin followed by DON and a-ZEA. The effects of both FB1 þ a-ZEA and NIVþ DON mixtures were also analysed to investigate possible interactions. The results indicated that combination of FB1þ a-ZEA produces a synergistic inhibition of porcine cell proliferation; whereas there is no interaction between DON and NIV on porcine wholeblood proliferation, at tested concentrations

Mycotoxins nivalenol and deoxynivalenol differently modulate cytokine mRNA expression in Jurkat T cells.

Deoxynivalenol (DON) and its hydroxylated form nivalenol (NIV) are Fusarium mycotoxins that occur in cereal grains alone or in combination. Several studies have shown that these metabolites affect lymphocyte functions. However, the molecular mechanisms underlying their activities are still partially known. To address this issue, we examined the influence of NIV and DON in modulating IFNc, IL-2 and IL-8 mRNA levels in Jurkat T cells. In PMA/ionomycin stimulated cells, pre-incubated with increasing concentrations of NIV, transcription was induced in the range 0.06–2 lM; higher concentrations of NIV were found non-stimulating (4 lM) or inhibitory (8 lM) for IFNc and IL-2 whereas IL-8 was still induced. DON administration elicited a similar profile for IL-8 and IFNc, whilst IL-2 mRNA was induced in a broader range of concentrations. Combination of NIV and DON at 1:1 and 1:10 ratios essentially restored the cytokine transcriptional pattern observed with NIV alone but the level of transcripts, with the exception of IL-8, peaked at lower concentrations suggesting interactive effects. Moreover both mycotoxins caused inhibition of cell proliferation, mediated by induction of apoptosis, confirming previous results and highlighting the usefulness of Jurkat as a T-cell model to study the effects of mycotoxins on the immune functions in humans

Trichothecenes NIV and DON modulate the maturation of murinedendritic cells

Nivalenol (NIV) and Deoxynivalenol (DON), mycotoxins of the trichothecene family are considered very common food contaminants. In this work, we investigated whether the immunotoxic effects ascribed to these trichothecenes may be mediated by perturbations in the activity of dendritic cells (DCs). Murine bone marrow-derived DCs were used to evaluate the effects of NIV and DON on the LPS-induced maturation process.We found that the expression of the class II MHC and of the accessory CD11c molecules, but not of the costimulatory CD86 marker, was down-regulated by NIV and DON exposure in LPS-treated DCs, as well as nitric oxide (NO) production. Interestingly, NIV, but not DON, induced DC necrosis. Moreover, the analysis of the cytokine pattern showed that IL-12 and IL-10 expressions induced by LPS exposure were suppressed by both trichothecenes in a dose-dependent fashion. On the other hand, the secretion of the proinflammatory cytokine TNFa was increased as a direct consequence of DON and NIV exposure. Taken together, our data indicated that the immunotoxicity of NIV and DON was related to the capacity of both trichothecenes to interfere with phenotypic and functional features of maturing DCs

Dynamics of Housing Debt in the Recent Boom and Great Recession

This paper documents a number of key facts about the evolution of mortgage debt, homeownership, debt burden, and subsequent delinquency during the recent housing boom and Great Recession. We show that the mortgage expansion was shared across the entire income distribution; that is, the flow and stock of debt rose across all income groups (except for the top 5%). The mortgage expansion was especially pronounced in areas with increased house prices, and the speed at which houses turned over (churn) in these areas went up significantly. However, the average loan-to-value ratios (LTV) at origination did not increase over the boom period. While homeownership rates increased for the middle- and upper-income households, there was no increase in homeownership for the lowest income groups. Finally, default rates postcrisis went up predominantly in areas with large house price drops, especially for high-income and high-FICO borrowers. These results are consistent with a view that the run-up in mortgage debt over the precrisis period was driven by rising home values and expectations of increasing prices