- Paper Report
- Open Access
PPAR-? ligands suppress arthritis in rats
- Kanneboyina Nagaraju1
© Current Science Ltd 2000
- Published: 28 September 2000
- Adjuvant-induced arthritis
- PPAR-? ligands
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcriptional factors of nuclear hormone receptor super family with some immunomodulatory properties. Various lipid or prostaglandin molecules have been proposed as natural PPAR-? ligands. Recent studies have shown that the PPAR-? ligands 15d-PGJ2, and troglitazone (a synthetic anti-diabetic) induce apoptosis in various cell types and inhibit nitric oxide (NO), tumor necrosis factor (TNF)-a, interleukin (IL)-1?, and IL-6 synthesis by antagonizing the activities of AP-1 and NF- B transcription factors. Therefore, the authors investigated the expression of PPAR-? in synovial tissues and in cultured synoviocytes of rheumatoid arthritis (RA) patients.
PPAR-? expression was detected in synovial tissues of all RA and OA patients in RA patients the expression was marked in macrophages and moderate in synovial cells , endothelial cells, and fibroblasts. The expression was lower in cells from OA patients. Untreated cultured synoviocytes showed both cytoplasmic and nuclear expression but 15d-PGJ2 treated cells showed nuclear translocation of PPAR-?. PPAR? mRNA and protein were produced by synoviocytes of RA patients and detected using RT-PCR and western blot analysis. PPAR-? ligands, troglitazone and 15d-PGJ2 effectively inhibited synoviocyte proliferation and induced classic apoptotic changes in these cells. Intraperitoneal administration of 15d-PGJ2 and troglitazone ameliorated AIA in Lewis Rats, suggesting that PPAR-? ligands have ani-inflammatory and growth-inhibitory effects on synovial cells without obvious side effects.
Synovial tissues from RA and osteoarthritis (OA) patients were used. Synovial tissues and cultured cells from these tissues were immunostained with anti-human PPAR- and the extent and intensity of staining was graded on various cell types. The PPAR- mRNA and protein expression was studied by RT-PCR and Western blotting. The cell proliferation and growth-inhibitory activities were studies by MTT assay. Apoptosis in cultured synovial cells was detected by Hoechst staining and propidium iodide. Female Lewis rats were used for arthritis induction and 15d-PGJ2or troglitazone treatment.