Applying blood-brain barrier in vitro models to study the influence of drugs on endothelial cells--effects of selected COX-inhibitors.
The influence of three cyclooxygenase (COX) inhibitors (indometacin, lornoxicam and celecoxib) with different COX-1/COX-2 profiles on endothelial cells using in vitro blood-brain barrier (BBB) models was investigated. For the experiments two BBB mimicking cell lines (PBMEC/C1-2 and ECV304) and primary human umbilical vein endothelial cells (HUVEC) were used. In preliminary tests the two cell lines and HUVEC were characterized by cell ELISA in respect of the presence of the tight junction proteins occludin and zonula occludens protein-1 (ZO-1), the adhesion molecules ICAM-1 and VCAM-1 and the endothelial marker von Willebrand factor (vWF). Then, the influence of indometacin, lornoxicam and celecoxib on the expression of occludin, ZO-1, ICAM-1 and vWF of the two cell lines and HUVEC was analysed by cell ELISA. The COX inhibitors caused an effect on PBMEC/C1-2 and HUVEC but no influence was observed on ECV304. The results of PBMEC/C1-2 and HUVEC indicated that in comparable therapeutical concentrations celecoxib had a higher potential to impair endothelial cells and to decrease the expression of occludin, ZO-1 and ICAM-1 than indometacin and lornoxicam.
Germann
B
B
Department of Medicinal Chemistry, University of Vienna, Austria.
Neuhaus
W
W
Hofer-Warbinek
R
R
Noe
C R
CR
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D000068579:Celecoxib; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis; D062793:Occludin; D010750:Phosphoproteins / Q000096:biosynthesis; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D062826:Zonula Occludens-1 Protein; D014841:von Willebrand Factor / Q000096:biosynthesis
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; D011720:Pyrazoles; D013449:Sulfonamides; C569042:TJP1 protein, human; C569044:Tjp1 protein, rat; D019010:Vascular Cell Adhesion Molecule-1; D062826:Zonula Occludens-1 Protein; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D000068579:Celecoxib; D007213:Indomethacin