Dataset Information

Proteomics study of a human thyrotoxicosis mode

ABSTRACT: In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. 16 healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 µg/d thyroxine p.o., as well as 4 and 8 weeks after stopping the application.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Elke Hammer

LAB HEAD: Uwe Völker

PROVIDER: PXD004815 | Pride | 2017-01-18

REPOSITORIES: Pride

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Publications

Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model.

Pietzner Maik M Engelmann Beatrice B Kacprowski Tim T Golchert Janine J Dirk Anna-Luise AL Hammer Elke E Iwen K Alexander KA Nauck Matthias M Wallaschofski Henri H Führer Dagmar D Münte Thomas F TF Friedrich Nele N Völker Uwe U Homuth Georg G Brabant Georg G

BMC medicine 20170109 1

<h4>Background</h4>Determinations of thyrotropin (TSH) and free thyroxine (FT<sub>4</sub>) represent the gold standard in evaluation of thyroid function. To screen for novel peripheral biomarkers of thyroid function and to characterize FT<sub>4</sub>-associated physiological signatures in human plasma we used an untargeted OMICS approach in a thyrotoxicosis model.<h4>Methods</h4>A sample of 16 healthy young men were treated with levothyroxine for 8 weeks and plasma was sampled before the intake ...[more]

PMID: 28065164

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Project description:Cytokines such as TNF-alpha and IL-1beta are known for their contribution to inflammatory processes in liver . In contrast, the cytokine IL-17 has not yet been assigned a role in liver diseases. IL-17 can cooperate with TNF-alpha to induce a synergistic response on several target genes in different cell lines, but no data exist for primary hepatocytes. To enhance our knowledge on the impact of IL-17 alone and combined with TNF-alpha in primary murine hepatocytes a comprehensive microarray study was designed. IL-1beta was included as this cytokine is suggested to act in a similar manner as the combination of TNF-alpha and IL-17, especially with respect to its role in mRNA stabilization. Results: The present microarray analysis demonstrates that primary murine hepatocytes responded to IL-17 stimulation by upregulation of chemokines and genes, which are functionally responsible to increase and sustain inflammation. Cxcl2, Nfkbiz and Zc3h12a were strongly induced, whereas the majority of the genes were only very moderately upregulated. Promoter analysis revealed involvement of NF-kappaB in the activation of many genes. Combined stimulation of TNF-alpha/IL-17 resulted in enhanced induction of gene expression, but significantly synergistic effects could be applied only to a few genes, such as Nfkbiz, Cxcl2, Zc3h12 and Steap4. Comparison of the gene expression profile obtained after stimulation of TNF-alpha/IL-17 versus IL-1 proposed a IL-1beta-like effect of the latter cytokine combination. Moreover, evidence was provided that modulation of mRNA stability may be a major mechanism by which IL-17 regulates gene expression in primary hepatocytes. This assumption was exemplarily proven for Nfkbiz mRNA for the first time in hepatocytes. Our studies also suggest that RNA stability can partially be correlated to the existence of AU rich elements, but further mechanisms like the RNase-activity of the upregulated Zc3h12a have to be considered. Conclusions: Our microarray analysis gives new insights in IL-17 induced gene expression in primary hepatocytes highlighting the crosstalk with the NF-kappaB signalling pathway. Gene expression profile suggests IL-17 a role in sustaining liver inflammatory processes most likely by RNA stabilization. Altogether, our results provide evidence that IL-17 alone and in concert with TNF-alpha may play a role in inflammatory liver diseases. Primary murine hepatocytes of three animals stimulated for 1 or 4h by TNF-alpha, IL-1beta, IL-17 or TNF-alpha followed by IL-17 were used for microarray analysis.

Dataset Information

Proteomics study of a human thyrotoxicosis mode

Publications

Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model.

Similar Datasets

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