Indirect co-cultivation of HepG2 with differentiated THP-1 cells induces AHR signalling and release of pro-inflammatory cytokines.

摘要: HepG2 and THP-1 cells, the latter differentiated by phorbol 12-myristate 13-acetate (PMA), were co-cultured characterized for typical liver-specific functions, such as xenobiotic detoxification, lipid cholesterol metabolism. Furthermore, liver injury-associated pathways, inflammation, studied. In general, co-cultivation of these cells produced a pro-inflammatory system, indicated increased levels cytokines (IL-8, TGF-α, IL-6, GM-CSF, G-CSF, TGF-β, hFGF) in respective supernatant. Increased expression target genes aryl hydrocarbon receptor (AHR), e.g., CYP1A1, CYP1A2 CYP1B1, detected, accompanied enzyme activity CYP1A1. Moreover, transcriptome analyses significant upregulation biosynthesis, which could be reduced to baseline lovastatin. contrast, total de novo synthesis was cells. Key events adverse outcome pathway (AOP) fibrosis activated co-cultivation, however, no increase concentration extracellular collagen detected. This indicates, that AOP should used with care. summary, indirect co-culture HepG2/THP-1 results an release cytokines, activation AHR enzymatic CYP1A activity.