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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 30, 2019 |
| Title |
High fat diet accelerates Barrett esophageal carcinogenesis by inducing a distinct IL-8 dependent immune reaction through alteration of the microbiome |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Barrett Esophagus (BE) is a risk factor for the development of esophageal adenocarcinoma (EAC). As endemic obesity emerges as a risk factor for increasing numbers of EAC we utilized our IL-1b mouse model of BE to understand the impact of a high fat diet (HFD) on disease progression. Indeed, increased dysplasia development in HFD treated IL-1b mice correlated with an accelerated cytokine response with specific upregulation of IL-8 in esophageal tissue, which could be confirmed by specific overexpression of IL-8 in the BE mouse model. Consequently we observed an influx of immature myeloid cells and neutrophils resulting in a decrease of regulatory NK T cells. HFD led to a specific shift in the gut microbiome, similar to that in human BE patients, being responsible for a specific inflammatory phenotype with elevated IL-1b and IL-8 which could be eliminated under germ free conditions and lead to an increased influx of cardia (Lgr5) stem cells into the esophagus giving rise to dysplasia.
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| Overall design |
Our mouse model of BE in which overexpression of IL-1b in the squamous esophagus induces chronic inflammation leads to metaplasia and dysplasia at the squamo-columnar junction (SCJ) in the mouse gastro-esophageal junction resembles the human disease. The impact of a high fat diet (HFD) and corresponding increase of specific upregulation of IL-8 in esophageal tissue on disease progression was investigated by comparing the gene expression profiles of mice overexpressing IL-1b and IL-8 and mice overexpressing IL-1b being fed with HFD or chow diet.
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| Contributor(s) |
Quante M, Wein F |
| Citation(s) |
30998992 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| U01 CA143056 |
Inflammation and the esophageal tumor microenvironment |
UNIVERSITY OF PENNSYLVANIA |
Timothy Cragin Wang |
| U54 CA163004 |
The Role of the Microenvironment in Barrett's Esophagus |
Trustees of Columbia University in the City of New York |
Timothy Cragin Wang |
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| Submission date |
Sep 07, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Michael Quante |
| E-mail(s) |
michael.quante@tum.de
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| Organization name |
Technische Universität München
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| Department |
II Medizinische Klinik
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| Street address |
Ismaninger Str 22
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| City |
München |
| ZIP/Postal code |
81675 |
| Country |
Germany |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (9)
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| GSM2776541 |
pl2Chow, 127, Cardia, 12mo |
| GSM2776542 |
pl2Chow, 130, Cardia, 12mo |
| GSM2776543 |
pl2Chow, 131, Cardia, 12mo |
| GSM2776544 |
pl2HFD, 123, Cardia, 12mo |
| GSM2776545 |
pl2HFD, 199, Cardia, 12mo |
| GSM2776546 |
pl2HFD, 202, Cardia, 12mo |
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| Relations |
| BioProject |
PRJNA402075 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE103616_RAW.tar |
44.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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