Endogenous prostaglandin E2 inhibits aberrant overgrowth of rheumatoid synovial tissue and the development of osteoclast activity through EP4 receptor
| Autor: | Toshiko Shibata-Nozaki, Hiroshi Ito, Hirofumi Mitomi, Takayuki Maruyama, So Nomoto, Hidehiro Yamada, Tatsuya Komagata, Toshiya Kanaji, Toshihito Mori, Shoichi Ozaki, Jun Akaogi |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Indomethacin Immunology Osteoclasts Pannus Dinoprostone Arthritis Rheumatoid Rheumatology Osteoclast Internal medicine medicine Humans Immunology and Allergy Macrophage Cyclooxygenase Inhibitors Pharmacology (medical) Prostaglandin E2 Receptor Cells Cultured Nitrobenzenes Sulfonamides Dose-Response Relationship Drug Chemistry Synovial Membrane medicine.disease In vitro Resorption medicine.anatomical_structure Endocrinology lipids (amino acids peptides and proteins) Receptors Prostaglandin E EP4 Subtype Ex vivo medicine.drug |
| Zdroj: | Arthritis & Rheumatism. 63:2595-2605 |
| ISSN: | 0004-3591 |
| Popis: | Objective We recently developed an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue. This study was undertaken to use that model to investigate the role of prostaglandin E2 (PGE2) and its receptor subtypes in the development of pannus growth and osteoclast activity in rheumatoid arthritis (RA). Methods Inflammatory cells that infiltrated pannus from patients with RA were collected without enzyme digestion and designated synovial tissue–derived inflammatory cells. Their single-cell suspensions were cultured in medium alone to observe an aberrant overgrowth of inflammatory tissue in vitro. Levels of cytokines produced in culture supernatants were measured using enzyme-linked immunosorbent assay kits. Osteoclast activity was assessed by the development of resorption pits in calcium phosphate–coated slides. Results Primary culture of the synovial tissue–derived inflammatory cells resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks, during which tumor necrosis factor α, PGE2, macrophage colony-stimulating factor, and matrix metalloproteinase 9 were produced in the supernatant. This aberrant overgrowth was inhibited by antirheumatic drugs including methotrexate and infliximab. On calcium phosphate–coated slides, synovial tissue–derived inflammatory cells showed numerous resorption pits. In the presence of inhibitors of endogenous prostanoid production such as indomethacin and NS398, exogenous PGE1 and EP4-specific agonists significantly inhibited all these activities of synovial tissue–derived inflammatory cells in a dose-dependent manner. Addition of indomethacin, NS398, or EP4-specific antagonist resulted in the enhancement of these cells' activities. EP2-specific agonist had a partial effect, while EP1- and EP3-specific agonists had no significant effects. Conclusion These results suggest that endogenous PGE2 produced in rheumatoid synovium negatively regulates aberrant synovial overgrowth and the development of osteoclast activity via EP4. |
| Databáze: | OpenAIRE |
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