Human neuronal cells expressed endogenous IFN-lambda 1 but not IFN-lambda 2/3. Upon the activation of Toll-like receptor (TLR)-3 expressed in the neuronal cells by polyriboinosinic polyribocytidylic acid (Polyl: C), both IFN-lambda 1 and IFN-lambda 2/3 expression was significantly induced. The activation of TLR-3 also Selleck Go6983 exhibited antiviral activity against pseudotyped human immunodeficiency virus (HIV)-1 infection of the neuronal cells. Human neuronal cells also expressed functional IFN-lambda receptor complex, interleukin-28 receptor a subunit (IL-28R alpha) and IL-10R beta, as evidenced by the observations that exogenous IFN-lambda treatment
inhibited pseudotyped HIV-1 infection of the neuronal cells and induced the expression of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)3G/3F, the newly identified anti-HIV-1 cellular factors. These data provide direct and compelling evidence that there is intracellular expression and regulation of IFN-lambda in human neuronal cells, which may have an important role in the innate neuronal protection against viral infections in the CNS. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The threshold of toxicologic concern (TTC) concept was developed as a method to identify a chemical intake level that is predicted to be without adverse human health effects assuming
daily intake over the course of a 70-yr life span. The TTC values are based on known structure-activity relationships and do not require chemical-specific toxicity data. This allows safety assessment (or prioritization for testing) of chemicals Mizoribine chemical structure Selleck MK-2206 with known molecular structure but little or no toxicity data. Recently, the TTC concept was extended to inhaled substances by converting a TTC expressed in micrograms per person per day to an airborne concentration (ng/m3), making allowance for intake by routes in addition to inhalation and implicitly
assuming 100% bioavailability of inhaled toxicants. The resulting concentration of no toxicologic concern (CoNTC), 30 ng/m3, represents a generic airborne concentration that is expected to pose no hazard to humans exposed continuously throughout a 70-yr lifetime. Published data on the levels of mycotoxins in agricultural dusts or in fungal spores, along with measured levels of airborne mycotoxins, spores, or dust in various environments, were used to identify conditions under which mycotoxin exposures might reach the CoNTC. Data demonstrate that airborne concentrations of dusts and mold spores sometimes encountered in agricultural environments have the potential to produce mycotoxin concentrations greater than the CoNTC. On the other hand, these data suggest that common exposures to mycotoxins from airborne molds in daily life, including in the built indoor environment, are below the concentration of no toxicologic concern.