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.

将HepG2和THP-1细胞（后者通过佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）分化）共培养，并针对典型的肝脏特异性功能（如异种生物排毒，脂质和胆固醇代谢）进行表征。此外，还研究了与肝脏损伤相关的途径，例如炎症。通常，这些细胞的共培养产生促炎系统，如细胞因子（IL-8，TGF-α，IL-6，GM-CSF，G-CSF，TGF-β和hFGF）。芳香烃受体（AHR），靶基因的增加的表达水平例如，CYP1A1，CYP1A2和CYP1B1被检测到，并伴有CYP1A1酶活性的增加。此外，转录组分析表明胆固醇生物合成明显上调，洛伐他汀可将其降低至基线水平。相反，在共培养的HepG2细胞中，从头合成脂质的总量减少了。共培养激活了纤维化不良结局途径（AOP）的关键事件，但是，未检测到细胞外胶原蛋白浓度的增加。这表明应谨慎使用AOP。总之，HepG2 / THP-1细胞的间接共培养导致促炎性细胞因子释放增加，AHR途径激活和酶促CYP1A活性增加。