Ciglitizone and 15d PGJ2 induce apoptosis in Jurkat and Raji cells
Carla Cristine Kanunfre1, Jofre Jacob da Silva Freitas, Celine Pompéia
1Department of Biology, State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
Abstract:
Several studies have shown that PPARgamma agonists play a role in the regulation of lymphocytes function and apoptosis. However, the molecular mechanism(s) underlying the immunomodulatory effects of PPARgamma agonists are not defined yet. In this study, the effects of PPARgamma (15d PGJ2 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 PGJ2 presented antiproliferative and cytotoxic effects on Jurkat and Raji cells as shown by [14C]-thymidine incorporation and cell viability assay. In addition, 15d PGJ2 inhibited cytokine production (IL-2 in Jurkat cells and IL-10 in Raji cells). The mechanism whereby PPARgamma agonists induced cytotoxicity is via apoptosis as shown by DNA fragmentation, nuclear condensation and phosphatidylserine externalization. The induction of apoptosis by ciglitizone and 15d PGJ2 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 PPARgamma agonists.
Insights
PPARgamma agonists like 15d PGJ2 and ciglitizone induce apoptosis in human T and B lymphocytes, suppressing proliferation and cytokine production. This mechanism involves decreased mitochondrial potential and c-myc expression.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists are known to modulate lymphocyte function and apoptosis.
- The precise molecular mechanisms behind these immunomodulatory effects remain largely undefined.
Purpose of the Study:
- To investigate the effects of PPARgamma ligands (15d PGJ2 and ciglitizone) on human T (Jurkat) and B (Raji) lymphocyte proliferation, cytokine production, and apoptosis.
- To elucidate the molecular pathways involved in PPARgamma agonist-induced lymphocyte apoptosis.
Main Methods:
- Assessing antiproliferative and cytotoxic effects using [14C]-thymidine incorporation and cell viability assays.
- Measuring cytokine production (IL-2, IL-10) in treated lymphocytes.
- Detecting apoptosis through DNA fragmentation, nuclear condensation, and phosphatidylserine externalization.
- Analyzing mitochondrial membrane potential and c-myc gene expression.
Main Results:
- Ciglitizone and 15d PGJ2 exhibited significant antiproliferative and cytotoxic effects on both Jurkat and Raji cells.
- 15d PGJ2 suppressed IL-2 production in Jurkat cells and IL-10 production in Raji cells.
- Cytotoxicity was mediated by apoptosis, characterized by DNA fragmentation, nuclear condensation, and phosphatidylserine externalization.
- Apoptosis induction correlated with decreased mitochondrial membrane potential and down-regulation of c-myc expression.
Conclusions:
- PPARgamma agonists (ciglitizone, 15d PGJ2) induce apoptosis in human T and B lymphocytes.
- Apoptosis is the likely mechanism underlying the observed suppression of proliferation and cytokine production.
- The findings highlight the role of mitochondrial membrane potential and c-myc down-regulation in PPARgamma agonist-induced lymphocyte apoptosis.
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