Activation-induced PPARgamma expression sensitizes primary human T cells toward apoptosis

J Leukoc Biol. 2003 May;73(5):665-72. doi: 10.1189/jlb.1002487.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydrazines / pharmacology
  • Jurkat Cells / cytology
  • Jurkat Cells / drug effects
  • Lymphocyte Activation / drug effects
  • Lymphopenia / immunology
  • Nitrogen Oxides
  • Phytohemagglutinins / pharmacology
  • Promoter Regions, Genetic / drug effects
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / pharmacology
  • Pyrimidines / pharmacology
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / biosynthesis
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / cytology*
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / agonists
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Cysteine Proteinase Inhibitors
  • Hydrazines
  • Nitrogen Oxides
  • Phytohemagglutinins
  • Pyrimidines
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • 1,1-diethyl-2-hydroxy-2-nitrosohydrazine
  • pirinixic acid
  • Prostaglandin D2
  • ciglitazone