PMID- 12165097
OWN - NLM
STAT- MEDLINE
DCOM- 20020911
LR  - 20190513
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 129
IP  - 2
DP  - 2002 Aug
TI  - Functional changes in rheumatoid fibroblast-like synovial cells through 
      activation of peroxisome proliferator-activated receptor gamma-mediated 
      signalling pathway.
PG  - 379-84
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand 
      dependent transcriptional factor known to be a regulator of adipogenesis. Recent 
      studies have also shown that stimulation of PPARgamma inhibits the 
      transcriptional activities of other nuclear factors and down-regulates 
      proinflammatory cytokine synthesis in T cells and monocytes. We examined, in the 
      present study, the functional significance of PPARgamma expressed in 
      fibroblast-like synovial cells (FLS) isolated from patients with rheumatoid 
      arthritis (RA). Incubation of FLS with a synthetic PPARgamma ligand, 
      troglitazone, inhibited endogenous production of TNF-alpha, IL-6 and IL-8, as 
      well as matrix metalloprotease-3 (MMP-3), without inducing apoptosis of the 
      cells. The gelatinase activity of FLS culture media was also inhibited by 
      troglitazone. Electrophoretic mobility shift assay (EMSA) showed a significant 
      reduction in the DNA binding activity of NF-kappaB in troglitazone-treated FLS in 
      response to TNF-alpha or IL-1beta. Moreover, long-term cultivation of FLS with 
      troglitazone resulted in morphological changes with marked lipid accumulation in 
      these cells. Our results show a negative regulatory function for PPARgamma on 
      cytokine and MMP production together with inhibition of cytokine-mediated 
      inflammatory responses in rheumatoid synovial cells. Our results also suggest 
      that FLS could differentiate into adipocyte-like cells in the presence of proper 
      stimulatory signals including PPARgamma.
FAU - Yamasaki, S
AU  - Yamasaki S
AD  - First Department of Internal Medicine, Nagasaki University School of Medicine, 
      1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
FAU - Nakashima, T
AU  - Nakashima T
FAU - Kawakami, A
AU  - Kawakami A
FAU - Miyashita, T
AU  - Miyashita T
FAU - Ida, H
AU  - Ida H
FAU - Migita, K
AU  - Migita K
FAU - Nakata, K
AU  - Nakata K
FAU - Eguchi, K
AU  - Eguchi K
LA  - eng
PT  - Journal Article
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Chromans)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Ligands)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-49-2 (DNA)
RN  - EC 3.4.24.- (Gelatinases)
RN  - I66ZZ0ZN0E (Troglitazone)
SB  - IM
MH  - Adipocytes/drug effects/pathology
MH  - Arthritis, Rheumatoid/genetics/immunology/*metabolism
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Chromans/metabolism
MH  - DNA/genetics/metabolism
MH  - Fibroblasts/drug effects/immunology/metabolism/pathology
MH  - Gelatinases/antagonists & inhibitors
MH  - Humans
MH  - In Vitro Techniques
MH  - Interleukin-6/biosynthesis
MH  - Interleukin-8/biosynthesis
MH  - Ligands
MH  - Matrix Metalloproteinase Inhibitors
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
MH  - Signal Transduction
MH  - Synovial Membrane/drug effects/immunology/*metabolism/pathology
MH  - Thiazoles/metabolism
MH  - *Thiazolidinediones
MH  - Transcription Factors/*metabolism
MH  - Troglitazone
MH  - Tumor Necrosis Factor-alpha/biosynthesis
PMC - PMC1906455
EDAT- 2002/08/08 10:00
MHDA- 2002/09/12 10:01
PMCR- 2003/08/01
CRDT- 2002/08/08 10:00
PHST- 2002/08/08 10:00 [pubmed]
PHST- 2002/09/12 10:01 [medline]
PHST- 2002/08/08 10:00 [entrez]
PHST- 2003/08/01 00:00 [pmc-release]
AID - 1876 [pii]
AID - 10.1046/j.1365-2249.2002.01876.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2002 Aug;129(2):379-84. doi: 10.1046/j.1365-2249.2002.01876.x.