title: Evaluation of the selected barrier properties of retinal pigment epithelial cell line ARPE-19 for an in-vitro blood-brain barrier model.
abstract: In-vitro models that maintain complex transport mechanisms and structural properties associated with the blood-brain barrier in vivo would be useful in drug permeability and neurotoxicological studies. To evaluate the suitability of a human retinal pigment epithelial cell line for a blood-brain barrier model, we have compared the barrier properties of the human retinal pigment epithelial cell line ARPE-19, the human colonic adenocarcinoma cell line Caco-2, and primary porcine microvessel endothelial cells. The tight junction proteins occludin and ZO-1 were stained immunocytochemically. The paracellular ionic permeability was evaluated by measuring the trans-epithelial or trans-endothelial electric resistance. To evaluate the active transport mechanisms, the existence and the activity of the efflux transporters, P-glycoprotein and multidrug resistance-associated proteins, were studied. All the cell types in this study stained positively for occludin and ZO-1. However, the trans-endothelial electric resistance of ARPE-19 cells was low compared with that of primary porcine microvessel endothelial cell and Caco-2 cells. In addition, both the P-glycoprotein expression and its activity in ARPE-19 cells were low. In conclusion, the barrier properties of the human ARPE-19 cell line were not satisfactory for a blood-brain barrier model. For future studies, it is important to develop a human brain endothelial cell line with expression of the complex in-vivo properties of the blood-brain barrier.
authors.affiliation: Medical School, Cell Research Center, University of Tampere, Finland. heidi.nevala@uta.fi
authors.forename: H
authors.initials: H
authors.lastname: Nevala
authors.forename: T
authors.initials: T
authors.lastname: Ylikomi
authors.forename: H
authors.initials: H
authors.lastname: Tähti
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D023401:Animal Use Alternatives; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D018938:Caco-2 Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D062826:Zonula Occludens-1 Protein
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007213:Indomethacin; D008565:Membrane Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D062793:Occludin; D010750:Phosphoproteins; D011339:Probenecid; D062826:Zonula Occludens-1 Protein; C513055:ABCB1 protein, human; C568985:OCLN protein, human; C569042:TJP1 protein, human; C421109:multidrug resistance-associated protein 1