Ciglitizone and 15d PGJ2 induce apoptosis in Jurkat and Raji cells.
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.
Kanunfre
Carla Cristine
CC
Department of Biology, State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
da Silva Freitas
Jofre Jacob
JJ
Pompéia
Celine
C
Gonçalves de Almeida
Débora Cristina
DC
Cury-Boaventura
Maria Fernanda
MF
Verlengia
Rozangela
R
Curi
Rui
R
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001562:Benzimidazoles; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D005456:Fluorescent Dyes; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D008024:Ligands; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists*; D010718:Phosphatidylserines / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*
C477819:15-deoxyprostaglandin J2; D017304:Annexin A5; D001562:Benzimidazoles; D002843:Chromatin; D016207:Cytokines; D005456:Fluorescent Dyes; D008024:Ligands; D047495:PPAR gamma; D010718:Phosphatidylserines; D012333:RNA, Messenger; D045162:Thiazolidinediones; C017807:bisbenzimide ethoxide trihydrochloride; D015230:Prostaglandin D2; C039671:ciglitazone