Effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the expression of inflammatory cytokines and apoptosis induction in rheumatoid synovial fibroblasts and monocytes

J Autoimmun. 2001 Nov;17(3):215-21. doi: 10.1006/jaut.2001.0542.


This study was performed to investigate whether peroxisome proliterator-activated receptor-gamma (PPAR-gamma) exerted an anti-inflammatory effect on rheumatoid synovial cells and inhibited dysregulated proliferation. The expression of PPAR-gamma mRNA in cultured human synoviocytes and THP-1 cells was analysed by RT-PCR. PPAR-gamma was expressed in normal, osteoarthritis (OA), rheumatoid arthritis (RA) synovial cells as well as a human monocytic cell line, THP-1. In RA and OA synoviocytes, the induction of inflammatory cytokine mRNA expression such as TNF-alpha and IL-1beta was significantly inhibited by the natural PPAR-gamma agonist, 15 deoxy-Delta(12,14)prostaglandin J(2)(15d-PGJ(2)). The effect of PPAR-gamma on the nuclear factor (NF)-kappaB activity was tested by electrophoretic mobility shift assay (EMSA). Both troglitazone and 15d-PGJ(2)markedly inhibited TNF-alpha-induced NF-kappaB activation at 30 microM. However, PPAR-gamma agonist neither reduced proliferation nor induced apoptosis in RA synoviocytes when measured by XTT assay and fluorescence activated cell sorter (FACS) analysis. In contrast, it induced apoptosis in a dose-dependent manner in THP-1 cells and augmented TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well. In conclusion, these data demonstrate that PPAR-gamma is expressed in human synoviocytes and THP-1 cells, and the PPAR-gamma activation inhibits expression of inflammatory cytokines in RA synoviocytes. Furthermore, PPAR-gamma activation induces apoptosis by itself and augments TRAIL/Apo2L-induced apoptosis in THP-1 cells. These results suggest that PPAR-gamma agonists may provide a new therapeutic approach for RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology*
  • Apoptosis Regulatory Proteins
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Fibroblasts / immunology*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Interleukin-1 / biosynthesis
  • Interleukin-1 / metabolism
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Microbodies / immunology
  • Microbodies / metabolism*
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Monocytes / pathology
  • NF-kappa B / metabolism
  • Osteoarthritis / immunology
  • Osteoarthritis / pathology
  • RNA, Messenger / biosynthesis
  • Receptors, Cytoplasmic and Nuclear / biosynthesis
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Synovial Membrane / immunology*
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • TNF-Related Apoptosis-Inducing Ligand
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology


  • Apoptosis Regulatory Proteins
  • Cytokines
  • Interleukin-1
  • Membrane Glycoproteins
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Transcription Factors
  • Tumor Necrosis Factor-alpha