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

ABSTRACT: The liver is composed of different cell populations. Interactions of different cell populations can be investigated bya 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 singlecultures, correlation networks(includingthe cytokinesG-CSF, CCL3, MCP-1, CCL20, FGF, TGF-β1, GM-CSF, IL-8 IL-6, IL-1β, and IL-18)were generated and the correlationswere validatedbyapplication of IL-8and TNF-α-neutralising antibodies. Thedata reveal that IL-8 is crucial for the interaction between hepatocytes and macrophages in vitro.In addition, transcriptome analyses showedthat a change in the ratio between macrophages and hepatocytes may triggerpro-inflammatory signalling pathways of the acute phase responseand the complement system(release of, e.g., certaincyto-and chemokines).Using diclofenac and LPS showed that the release of cytokines is increasingwith higher ratios of MDMs. Altogether we coulddemonstratethat the current co-culture system is better suited to mirror thein vivosituation when compared to previously established co-culturesystems composed of HepG2and differentiated THP-1cells.Further, our data reveal that the cytokine IL-8 is crucial for the interaction between hepatocytes and macrophages in vitro.

ORGANISM(S): Homo sapiens

PROVIDER: GSE156627 | GEO | 2021/03/19

REPOSITORIES: GEO

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