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

Jong Dae Ji, Hyeonjoo Cheon, Jae Bum Jun, Seong Jae Choi, Ye Ree Kim, Young Ho Lee, Tae Hwan Kim, In Jeong Chae, Gwan Gyu Song, Dae Hyun Yoo, Seong Yoon Kim, Jeongwon Sohn

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61 Citations (Scopus)

Abstract

This study was performed to investigate whether peroxisome proliterator-activated receptor-γ (PPAR-γ) exerted an anti-inflammatory effect on rheumatoid synovial cells and inhibited dysregulated proliferation. The expression of PPAR-γ mRNA in cultured human synoviocytes and THP-1 cells was analysed by RT-PCR. PPAR-γ was expressed in normal, osteoarthritis (OA), rheumatoid arthritis (RA) synovial cells as well as a human monocytic cell line, THP-1. In RA and GA synoviocytes, the induction of infammatory cytokine mRNA expression such as TNF-α and IL-1β was significantly inhibited by the natural PPAR-γ agonist, 15 deoxy-Δ12,14 prostaglandin J2 (15d-PGJ2). The effect of PPAR-γ on the nuclear factor (NF)-κB activity was tested by electrophoretic mobility shift assay (EMSA). Both troglitazone and 15d-PGJ2 markedly inhibited TNF-α-induced NF-κB activation at 30 μM. However, PPAR-γ 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-γ is expressed in human synoviocytes and THP-1 cells, and the PPAR-γ activation inhibits expression of inflammatory cytokines in RA synoviocytes. Furthermore, PPAR-γ activation induces apoptosis by itself and augments TRAIL/Apo2L-induced apoptosis in THP-1 cells. These results suggest that PPAR-γ agonists may provide a new therapeutic approach for RA.

Original languageEnglish
Pages (from-to)215-221
Number of pages7
JournalJournal of Autoimmunity
Volume17
Issue number3
DOIs
Publication statusPublished - 2001 Nov 1

Keywords

  • Apoptosis
  • Inflammatory cytokine
  • NF-κB
  • PPAR-γ
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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