Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model

Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver

“…Studies dealing with the effects of TZDs on gene expression in either primary human hepatocyte cultures or human hepatoma cell lines are scarce and most of them studied only few genes [76, 79] (Table 2). Human hepatocytes were slightly more sensitive than their rat counterparts [34], but less sensitive than human hepatoma HepG2 cells to cytotoxicity induced by TRO, supporting the conclusion of an absence of correlation between TRO toxicity and its hepatic metabolism.…”

Synthetic isoforms of endogenous sulfatides differently modulate indoleamine 2,3-dioxygenase in antigen presenting cells

“…2 shows that the synthetic sulfatide isoforms (see Fig. 1) differently affect the basal level of IDO1 mRNA expression in human CD1d-transfected THP-1 cells, a useful model for studying the activation of immune cells (Edling et al, 2009). The quantification of the gene transcription by semi-quantitative PCR demonstrated that the cellular basal expression of IDO1 was significantly increased after (24 h) cell treatment with 1000 U/ml IFN-γ (positive control), while it resulted reduced after C16:0 sulfatide (−48 ± 3% at 0.01 μΜ over compound-untreated cells; n = 3) ( Fig.…”

Terbinafine stimulates the pro-inflammatory responses in human monocytic THP-1 cells through an ERK signaling pathway

“…Ximelagatran increased the release of chemokines from THP-1 cells but the types of released cytokines and the time course of the cytokine release by the drug treatment were different from the case of terbinafine (Edling et al 2008). In addition, troglitazone increased the mRNA expression levels of pro-inflammatory cytokines and chemokines in THP-1 cells, and some of them were affected by co-culture with human hepatoma Huh-7 cells (Edling et al 2009). Therefore, measurement of the release of pro-inflammatory cytokines and chemokines from human monocytic cells may be useful to predict adverse reactions to drugs involving immune-mediated hepatic injury.…”

“…In human monocytic THP-1 cells, the mRNA expression levels and/or the release of pro-inflammatory cytokines and chemokines were increased by the treatment with troglitazone or ximelagatran (Edling et al 2008;Edling et al 2009). …”