Cytokines regulate fibroblast-like synovial cell differentiation to adipocyte-like cells.

Abstract

OBJECTIVES:

Our recent work showed that fibroblast-like synovial cells (FLS) could differentiate into adipocyte-like cells in vitro in response to stimulation with peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand. The aim of the present study was to determine the role of cytokines in the regulation of FLS differentiation to adipocyte-like cells.

METHODS:

FLS isolated from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and from normal synovial tissues were incubated with the synthetic PPAR gamma ligand troglitazone to induce adipocyte-like differentiation of the cells.

RESULTS:

Production of interleukin (IL)-6, IL-8 and matrix metalloproteinase-3 was reduced in adipocyte-like cells compared with FLS. DNA binding activity of nuclear factor kappa B (NF-kappa B) was clearly inhibited in adipocyte-like cells. Cultivation of FLS with interferon gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) or IL-1 beta inhibited the expression of PPAR gamma as well as CCAAT/enhancer binding protein (C/EBP) nuclear activity, and thus suppressed adipocyte-like cell differentiation in vitro.

CONCLUSION:

Our results indicate the importance of PPAR gamma and C/EBP in adipocyte-like cell differentiation of FLS and that the process is influenced by inflammatory cytokines, and suggest that the proinflammatory character of FLS in patients with RA is diminished during adipocyte-like cell differentiation.

• Authors: S Yamasaki, T Nakashima, A Kawakami, T Miyashita, F Tanaka, H Ida, K Migita, T Origuchi, K Eguchi
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 43 Issue 4 Pg. 448-52 (Apr 2004) ISSN: 1462-0324 [Print] England
• PMID: 14734788 (Publication Type: Journal Article)

Chemical References

• Chromans
• Cytokines
• Interleukin-6
• Interleukin-8
• Receptors, Cytoplasmic and Nuclear
• Thiazolidinediones
• Transcription Factors
• Matrix Metalloproteinase 3
• Troglitazone

Topics

• Adipocytes (metabolism, pathology)
• Arthritis, Rheumatoid (pathology)
• Cell Differentiation (drug effects, physiology)
• Cells, Cultured
• Chromans (pharmacology)
• Cytokines (physiology)
• Fibroblasts (pathology)
• Humans
• Interleukin-6 (biosynthesis)
• Interleukin-8 (biosynthesis)
• Matrix Metalloproteinase 3 (biosynthesis)
• Osteoarthritis (pathology)
• Receptors, Cytoplasmic and Nuclear (metabolism)
• Synovial Membrane (pathology)
• Thiazolidinediones (pharmacology)
• Transcription Factors (metabolism)
• Troglitazone