Ciglitizone and 15d PGJ 2 induce apoptosis in Jurkat and Raji cells

Abstract

Several studies have shown that PPARγ agonists play a role in the regulation of lymphocytes function and apoptosis. However, the molecular mechanism(s) underlying the immunomodulatory effects of PPARγ agonists are not defined yet. In this study, the effects of PPARγ (15d PGJ 2 and ciglitizone) ligands on proliferation, cytokine production and apoptosis of Jurkat and Raji cells (human T and B lymphocytes, respectively) were examined. Ciglitizone and 15d PGJ 2 presented antiproliferative and cytotoxic effects on Jurkat and Raji cells as shown by [ 14C]-thymidine incorporation and cell viability assay. In addition, 15d PGJ 2 inhibited cytokine production (IL-2 in Jurkat cells and IL-10 in Raji cells). The mechanism whereby PPARγ agonists induced cytotoxicity is via apoptosis as shown by DNA fragmentation, nuclear condensation and phosphatidylserine externalization. The induction of apoptosis by ciglitizone and 15d PGJ 2 on Jurkat and Raji cells may explain the suppression of cytokine production and the decrease in proliferation observed in both cell types. The apoptotic process was associated with a decrease in mitochondrial membrane potential and a marked down-regulation of the c-myc expression. These findings might play a key role in the apoptosis of T and B lymphocytes induced by PPARγ agonists.