Article CC BY 4.0
refereed
published

Novel indirect co-culture of immortalised hepatocytes with monocyte derived macrophages is characterised by pro-inflammatory cytokine networks

Affiliation
German Federal Institute for Risk Assessment (BfR), Department 7 Chemical and Product Safety, Unit 72 Chemicals Safety, Germany
Padberg, Florian;
Affiliation
German Federal Institute for Risk Assessment (BfR), Department 5 Food Safety, Unit 51 Effect-based Analytics and Toxicogenomics, Germany
Höper, Tessa;
Affiliation
BioControl Jena GmbH, Hans-Knöll-Straße 6, Jena, Germany
Henkel, Sebastian;
Affiliation
BioControl Jena GmbH, Hans-Knöll-Straße 6, Jena, Germany
Driesch, Dominik;
Affiliation
German Federal Institute for Risk Assessment (BfR), Department 7 Chemical and Product Safety, Germany
Luch, Andreas;
Affiliation
German Federal Institute for Risk Assessment (BfR), Department 7 Chemical and Product Safety, Unit 74 Safety of Food-Contact Materials, Germany
Zellmer, Sebastian

The liver is composed of different cell populations. Interactions of different cell populations can be investigated by a newly established indirect co-culture system consisting of immortalised primary human hepatocytes and human monocyte derived macrophages (MDMs). Using the time-dependent cytokine secretion of the co-cultures and single cultures, correlation networks (including the cytokines G-CSF, CCL3, MCP-1, CCL20, FGF, TGF-β1, GM-CSF, IL-8 IL-6, IL-1β, and IL-18) were generated and the correlations were validated by application of IL-8 and TNF-α-neutralising antibodies. The data reveal that IL-8 is crucial for the interaction between hepatocytes and macrophages in vitro. In addition, transcriptome analyses showed that a change in the ratio between macrophages and hepatocytes may trigger pro-inflammatory signalling pathways of the acute phase response and the complement system (release of, e.g., certain cyto- and chemokines). Using diclofenac and LPS showed that the release of cytokines is increasing with higher ratios of MDMs. Altogether, we could demonstrate that the current co-culture system is better suited to mirror the in vivo situation when compared to previously established co-culture systems composed of HepG2 and differentiated THP-1 cells. Further, our data reveal that the cytokine IL-8 is crucial for the interaction between hepatocytes and macrophages in vitro.

Cite

Citation style:
Could not load citation form.

Access Statistic

Total:
Downloads:
Abtractviews:
Last 12 Month:
Downloads:
Abtractviews:

Rights

Use and reproduction: