Activation-induced PPARgamma expression sensitizes primary human T cells toward apoptosis.
Phytohemagglutinin (PHA) elicited expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in primary human T cells via the PPARgamma3 promoter, as shown by reverse transcription-polymerase chain reaction. Electrophoretic mobility shift assay demonstrated no correlation between PPARgamma expression and its activation. However, addition of specific PPARgamma agonists such as ciglitazone or 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) for 1 h following PHA pretreatment provoked PPARgamma activation verified by supershift analysis. Taking the proapoptotic properties of PPARgamma into consideration, we analyzed induction of apoptosis in activated T cells in response to PPARgamma agonists. Cells exposed to PPARgamma agonists alone revealed minor cell death compared with controls, whereas treatment with 15d-PGJ(2) or ciglitazone for 4 h subsequent to PHA stimulation significantly increased cell demise, which was attenuated by the pan-caspase inhibitor zVAD, pointing to apoptosis as the underlying mechanism. These data may be relevant for pathophysiological conditions accompanied with lymphopenia of T cells under conditions such as sepsis.
Tautenhahn
Anja
A
University of Kaiserslautern, Institute of Cell Biology, Erwin-Schroedinger-Strasse, Germany.
Brüne
Bernhard
B
von Knethen
Andreas
A
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D019169:Jurkat Cells / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008231:Lymphopenia / Q000276:immunology; D009589:Nitrogen Oxides; D010835:Phytohemagglutinins / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D015853:Cysteine Proteinase Inhibitors; D006834:Hydrazines; D009589:Nitrogen Oxides; D010835:Phytohemagglutinins; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; C006253:pirinixic acid; D015230:Prostaglandin D2; C039671:ciglitazone