The overall goals of this Project are to determine how selected Superfund chemicals influence immunity and inflammation and to understand the mechanisms and potential health consequences of such effects.
The aims for the next granting period were driven by a need for knowledge of interactions among chemicals and the specific and nonspecific components of the immune system. Specific hypotheses to be tested derive from the recent findings of the investigators of the three subprojects. This Subproject is a new addition based on the observation that administration to animals of certain hepatotoxicants at doses that cause modest liver pathology results in release of a serum factor that is immunosuppressive. Recently, this factor has been identified as transforming growth factor-beta(TGF-beta). During the next granting period, a battery of functional assays will be used to determine whether alterations in immunocompetence are mediated by TGF-beta alone or involve other factors, such as overproduction of interleukin-2 by helper T-cells. The studies proposed in this Project will employ cellular, isolated organ and whole animal models and entail molecular, biochemical and morphologic methods that include techniques such as cell imaging and flow cytometry. Accomplishing goals of this Project as well as aiding in the toxicologic evaluation of products of remediation will involve considerable interaction not only among Project investigators but also with investigator of other projects and cores. Results from these studies will increase understanding of the mechanisms and potential health consequences of interactions of Superfund chemicals with the immune system.
|Nault, Rance; Doskey, Claire M; Fader, Kelly A et al. (2018) Comparison of Hepatic NRF2 and Aryl Hydrocarbon Receptor Binding in 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Treated Mice Demonstrates NRF2-Independent PKM2 Induction. Mol Pharmacol 94:876-884|
|Dornbos, Peter; LaPres, John J (2018) Incorporating population-level genetic variability within laboratory models in toxicology: From the individual to the population. Toxicology 395:1-8|
|Zhang, Shuai; Liu, Qinfu; Gao, Feng et al. (2018) Interfacial Structure and Interaction of Kaolinite Intercalated with N-methylformamide Insight from Molecular Dynamics Modeling. Appl Clay Sci 158:204-210|
|Fader, Kelly A; Nault, Rance; Raehtz, Sandi et al. (2018) 2,3,7,8-Tetrachlorodibenzo-p-dioxin dose-dependently increases bone mass and decreases marrow adiposity in juvenile mice. Toxicol Appl Pharmacol 348:85-98|
|Zhang, Shuai; Liu, Qinfu; Cheng, Hongfei et al. (2018) Mechanism Responsible for Intercalation of Dimethyl Sulfoxide in Kaolinite: Molecular Dynamics Simulations. Appl Clay Sci 151:46-53|
|Zhang, Qiang; Li, Jin; Middleton, Alistair et al. (2018) Bridging the Data Gap From in vitro Toxicity Testing to Chemical Safety Assessment Through Computational Modeling. Front Public Health 6:261|
|Fader, K A; Nault, R; Kirby, M P et al. (2018) Corrigendum to ""Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERB?/? activation in aryl hydrocarbon receptor-elicited hepatotoxicity"" [Toxicol. Appl. Pharmacol. 321 (2017) 1-17]. Toxicol Appl Pharmacol 344:74|
|Konganti, Kranti; Ehrlich, Andre; Rusyn, Ivan et al. (2018) gQTL: A Web Application for QTL Analysis Using the Collaborative Cross Mouse Genetic Reference Population. G3 (Bethesda) 8:2559-2562|
|Zhang, Shuai; Liu, Qinfu; Gao, Feng et al. (2018) Molecular Dynamics Simulation of Basal Spacing, Energetics, and Structure Evolution of a Kaolinite-Formamide Intercalation Complex and Their Interfacial Interaction. J Phys Chem C Nanomater Interfaces 122:3341-3349|
|Phadnis-Moghe, Ashwini S; Kaminski, Norbert E (2017) Immunotoxicity testing using human primary leukocytes: An adjunct approach for the evaluation of human risk. Curr Opin Toxicol 3:25-29|
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