J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M400049-JLR200 on August 16, 2004

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Journal of Lipid Research, Vol. 45, 2015-2024, November 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Rosiglitazone upregulates caveolin-1 expression in THP-1 cells through a PPAR-dependent mechanism

Gemma Llaverias*, Manuel Vázquez-Carrera*, Rosa M. Sánchez*, Véronique Noé{dagger}, Carlos J. Ciudad{dagger}, Juan C. Laguna* and Marta Alegret1,*

* Unitat de Farmacologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain
{dagger} Departament de Bioquímica i Biologia Molecular, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain

1 To whom correspondence should be addressed. e-mail: alegret{at}ub.edu

Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) 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.

Abbreviations: cav-1, caveolin-1; EMSA, electrophoretic mobility shift analysis; LXR, liver X receptor; PPAR{gamma}, peroxisome proliferator-activated receptor {gamma}; PPRE, peroxisome proliferator response element; RXR, 9-cis-retinoic acid receptor

Supplementary key words peroxisome proliferator-activated receptors • thiazolidinediones • macrophage • human • liver X receptor


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