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.

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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