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| Status |
Public on Aug 06, 2020 |
| Title |
Indirect co-cultivation of HepG2 with differentiated THP-1 cells induces AHR signalling and release of pro-inflammatory cytokines. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
HepG2 and THP-1 cells, the latter differentiated by phorbol 12-myristate 13-acetate (PMA), were co-cultured and characterized for typical liver-specific functions, such as xenobiotic detoxification, lipid and cholesterol metabolism. Furthermore, liver injury-associated pathways, such as inflammation, were studied. In general, the co-cultivation of these cells produced a pro-inflammatory system, as indicated by increased levels of cytokines (IL-8, TGF-α, IL-6, GM-CSF, G-CSF, TGF-β, and hFGF) in the respective supernatant. Increased expression levels of target genes of the aryl hydrocarbon receptor (AHR), e.g., CYP1A1, CYP1A2 and CYP1B1, were detected, accompanied by the increased enzyme activity of CYP1A1. Moreover, transcriptome analyses indicated a significant upregulation of cholesterol biosynthesis, which could be reduced to baseline levels by lovastatin. In contrast, total de novo lipid synthesis was reduced in co-cultured HepG2 cells. Key events of the adverse outcome pathway (AOP) for fibrosis were activated by the co-cultivation, however, no increase in the concentration of extracellular collagen was detected. This indicates, that AOP should be used with care. In summary, the indirect co-culture of HepG2/THP 1 cells results in an increased release of pro-inflammatory cytokines, an activation of the AHR pathway and an increased enzymatic CYP1A activity.
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| Overall design |
Characterisation of HepG2 cells under influence of PMA-differentiated THP-1 cells using the Affymetrix Human Clariom S. Array data was processed by the company ATLAS Biolabs GmbH (Friedrichstraße 147, 10117 Berlin, Germany). Five biological replicates were performed for each condition.
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| Contributor(s) |
Padberg F, Hering H, Luch A, Zellmer S |
| Citation(s) |
32739440 |
| Submission date |
Nov 08, 2019 |
| Last update date |
Aug 06, 2020 |
| Contact name |
Florian Padberg |
| Organization name |
German Federal Institute for Risk Assessment (BfR)
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| Department |
Chemicals and Product Safety
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| Street address |
Max-Dohrn-Strasse 8-10
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| City |
Berlin |
| ZIP/Postal code |
10589 |
| Country |
Germany |
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| Platforms (1) |
| GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA588420 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE140141_RAW.tar |
13.4 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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