Rosiglitazone upregulates caveolin-1 expression in THP-1 cells through a PPAR-dependent mechanism.
Peroxisome proliferator-activated receptor gamma (PPARgamma) activation or overexpression induces caveolin-1 (cav-1) expression in several cell types. The objective of this study was to investigate if PPAR agonists could also regulate the cav-1 gene in macrophages and to explore the mechanisms involved. Our experiments demonstrated that rosiglitazone dose- and time-dependently increased cav-1 mRNA and protein in THP-1 macrophages. This induction was not observed in the presence of inhibitors of transcription or de novo protein synthesis. We also showed that the increase in cav-1 elicited by rosiglitazone was not related either to macrophage differentiation or to cellular apoptosis. The inductive effect seems to be dependent on PPAR activation, as the PPAR antagonist GW9662 abolished it. The activation of the liver X receptor with 22(R)-hydroxycholesterol also increased cav-1 mRNA, whereas the inactive (S) isomer did not. Finally, we identified a functional peroxisome proliferator response element in the cav-1 promoter that was activated upon rosiglitazone treatment in THP-1 macrophages.
Unitat de Farmacologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.
Gemma
G
Llaverias
Manuel
M
Vázquez-Carrera
Rosa M
RM
Sánchez
Véronique
V
Noé
Carlos J
CJ
Ciudad
Juan C
JC
Laguna
Marta
M
Alegret
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D039481:CD11b Antigen / Q000096:biosynthesis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D051242:Caveolin 1; D022461:Caveolins / Q000096:biosynthesis* / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D008024:Ligands; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000077154:Rosiglitazone; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D014158:Transcription, Genetic; D015854:Up-Regulation; D014665:Vasodilator Agents / Q000494:pharmacology*
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; C495540:CAV1 protein, human; D039481:CD11b Antigen; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D000077154:Rosiglitazone; C003585:22-hydroxycholesterol; D012313:RNA; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D013755:Tetradecanoylphorbol Acetate