A transgenic rat hepatocyte - Kupffer cell co-culture model for evaluation of direct and macrophage-related effect of poly(amidoamine) dendrimers
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Tartalom: http://real.mtak.hu/45578/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published


Type = Article
Cím:
A transgenic rat hepatocyte - Kupffer cell co-culture model for evaluation of direct and macrophage-related effect of poly(amidoamine) dendrimers
Létrehozó:
Jemnitz, Katalin
Bátai-Konczos, Attila
SzabĂł, MĂłnika
Ioja, Enikő
Kolacsek, Orsolya
Orbán, Tamás I.
Török, György
Homolya, László
Veres, Zsuzsa
Kiadó:
Elsevier
Dátum:
2017
Téma:
QH3011 Biochemistry / biokémia
RM Therapeutics. Pharmacology / terápia, gyógyszertan
Tartalmi leírás:
Increasing number of papers demonstrate that Kupffer cells (KCs) play a role in the development of drug induced liver injury (DILI). Furthermore, elevated intracellular Ca2+ level of hepatocytes is considered as a common marker of DILI. Here we applied an in vitro model based on hepatocyte mono- and hepatocyte/KC co-cultures (H/KC) isolated from transgenic rats stably expressing the GCaMP2 fluorescent Ca2+ sensor protein to investigate the effects of polycationic (G5), polyanionic (G4.5) and polyethylene-glycol coated neutral (G5 Peg) dendrimers known to accumulate in the liver, primarily in KCs. Following dendrimer exposure, hepatocyte homeostasis was measured by MTT cytotoxicity assay and by Ca2+ imaging, while hepatocyte functions were studied by CYP2B1/2 inducibility, and bilirubin and taurocholate transport. G5 was significantly more cytotoxic than G4.5 for hepatocytes and induced Ca2+ oscillation and sustained Ca2+ signals at 1muM and10 muM, respectively both in hepatocytes and KCs. Dendrimer-induced Ca2+ signals in hepatocytes were attenuated by macrophages. Activation of KCs by lipopolysaccharide and G5 decreased the inducibility of CYP2B1/2, which was restored by depleting the KCs with gadolinium-chloride and pentoxyphylline, suggesting a role of macrophages in the hindrance of CYP2B1/2 induction by G5 and lipopolysaccharide. In the H/KC, but not in the hepatocyte mono-culture, G5 reduced the canalicular efflux of bilirubin and stimulated the uptake and canalicular efflux of taurocholate. In conclusion, H/KC provides a good model for the prediction of hepatotoxic potential of drugs, especially of nanomaterials known to be trapped by macrophages, activation of which presumably contributes to DILI.
Nyelv:
angol
Típus:
Article
PeerReviewed
info:eu-repo/semantics/article
Formátum:
text
Azonosító:
Jemnitz, Katalin and Bátai-Konczos, Attila and Szabó, Mónika and Ioja, Enikő and Kolacsek, Orsolya and Orbán, Tamás I. and Török, György and Homolya, László and Veres, Zsuzsa (2017) A transgenic rat hepatocyte - Kupffer cell co-culture model for evaluation of direct and macrophage-related effect of poly(amidoamine) dendrimers. Toxicology in Vitro, 38. pp. 159-169. ISSN 0887-2333
Kapcsolat:
MTMT:3148042; doi:10.1016/j.tiv.2016.09.016