Effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the expression of inflammatory cytokines and apoptosis induction in rheumatoid synovial fibroblasts and monocytes
| Autor: | Seong Jae Choi, Jong Dae Ji, Young Ho Lee, Ye Ree Kim, Jae-Bum Jun, In Jeong Chae, Gwan Gyu Song, Dae Hyun Yoo, Jeongwon Sohn, Tae-Hwan Kim, Hyeonjoo Cheon, Seong Yoon Kim |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Immunology Receptors Cytoplasmic and Nuclear Inflammation Apoptosis Biology Microbodies Monocytes Proinflammatory cytokine Arthritis Rheumatoid TNF-Related Apoptosis-Inducing Ligand Internal medicine Osteoarthritis medicine Immunology and Allergy Humans RNA Messenger Cells Cultured Membrane Glycoproteins Tumor Necrosis Factor-alpha Monocyte Synovial Membrane NF-kappa B Fibroblasts Cytokine medicine.anatomical_structure Endocrinology Cell culture Cancer research Cytokines lipids (amino acids peptides and proteins) Tumor necrosis factor alpha medicine.symptom Synovial membrane Apoptosis Regulatory Proteins Interleukin-1 Transcription Factors |
| Zdroj: | Journal of autoimmunity. 17(3) |
| ISSN: | 0896-8411 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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