Differential modulation of cell cycle, apoptosis and PPARγ2 gene expression by PPARγ agonists ciglitazone and 9-hydroxyoctadecadienoic acid in monocytic cells

We sought to compare the effects of the thiazolidinedione ciglitazone with the endogenous fatty acid PPARγ agonists 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE), in U937 monocytic cells. Ciglitazone and 9-HODE inhibited cell proliferation and all three agonists increased cellular content of C18:0 fatty acids. Ciglitazone and 13-HODE resulted in an increased percentage of cells in S phase and ciglitazone reduced the percentage of cells in G2/M phase of cell cycle, whilst 9-HODE increased the percentage of cells in G0/1 and reduced the fraction in S and G2/M phases. 9-HODE selectively induced apoptosis in U937 cells, and increased PPARγ2 gene expression. Induction of apoptosis by 9-HODE was not abrogated by the presence of the PPARγ antagonist GW9662. Synthetic (TZD) and endogenous fatty acid ligands for PPARγ, ciglitazone and 9- and 13-HODE, possess differential, ligand specific actions in monocytic cells to regulate cell cycle progression, apoptosis and PPARγ2 gene expression.