PPAR-α Agonist WY-14643 Inhibits LPS-Induced Inflammation in Synovial Fibroblasts via NF-kB Pathway

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• 作者：Degang Huang ; Quanlai Zhao ; Hongfei Liu ; Yongjie Guo…
• 刊名：Journal of Molecular Neuroscience
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：59
• 期：4
• 页码：544-553
• 全文大小：2,454 KB
• 刊物主题：Neurosciences; Neurochemistry; Cell Biology; Proteomics; Neurology;
• 出版者：Springer US
• ISSN：1559-1166
• 卷排序：59

文摘

Osteoarthritis (OA), the most prevalent form of arthritis that results from breakdown of joint cartilage and underlying bone, has been viewed as a chronic condition manifested by persistence of inflammatory responses and infiltration of lymphocytes. Regulation of the inflammatory responses in synovial fibroblasts might be useful to prevent the development and deterioration of osteoarthritis. WY-14643, a potent peroxisome proliferator activator receptor-α (PPAR-α) agonist, has been described to beneficially regulate inflammation in many mammalian cells. Here, we investigate the potential anti-inflammatory role of WY-14643 in lipopolysaccharide (LPS)-induced synovial fibroblasts. WY-14643 greatly inhibited the production of NO and PGE₂ induced by LPS. In addition, the mRNA expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelin-1 (ET-1), and tissue factor (TF) was significantly suppressed by WY-14643, as well as the secretion of pro-inflammatory cytokines including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1). Furthermore, the transcription activity and nuclear translocation of NF-kB were found to be markedly decreased by WY-14643, while the phosphorylation of IkB was enhanced, indicating that the anti-inflammatory role of WY-14643 was meditated by NF-kB-dependent pathway. The application of WY-14643 failed to carry out its anti-inflammatory function in PPAR-α silenced cells, suggesting the role of PPAR-α. These findings may facilitate further studies investigating the translation of pharmacological PPAR-α activation into clinical therapy of OA.KeywordsWY-14643OsteoarthritisSynovial fibroblastsInflammationNF-kB