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Series GSE19272 Query DataSets for GSE19272
Status Public on Mar 01, 2010
Title Genome-wide comparison between IL-17 and combined TNF-alpha/ IL-17 induced genes in primary murine hepatocytes
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
Overall design 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.
Contributor(s) Sparna T, Retéy J, Schmich K, Albrecht U, Naumann K, MacNelly S, von Weizsäcker F, Gretz N, Fischer H, Timmer J, Bode J, Merfort I
Citation(s) 20374638
Submission date Dec 02, 2009
Last update date Feb 11, 2019
Contact name Irmgard Merfort
Organization name University of Freiburg - Institute of Pharmaceutical Science
Department Department of Pharmaceutical Biology and Biotechnology
Lab Merfort
Street address Stefan-Meier-Str. 19
City Freiburg
State/province BW
ZIP/Postal code 79104
Country Germany
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (30)
GSM478094 1_1_Control_1h_rep1
GSM478095 1_3_IL1b_1h_rep1
GSM478096 1_5_TNFa_1h_rep1
BioProject PRJNA120949

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Supplementary file Size Download File type/resource
GSE19272_RAW.tar 177.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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