Down-regulating peroxisome proliferator-activated receptor-gamma coactivator-1beta alleviates the proinflammatory effect of rheumatoid arthritis fibroblast-like synoviocytes through inhibiting extracellular signal-regulated kinase, p38 and nuclear factor-kappaB activation

作者：Zhou, Jing-Jing; Ma, Jian-Da; Mo, Ying-Qian; Zheng, Dong-Hui; Chen, Le-Feng; Wei, Xiu-Ning; Dai, Lie^*

来源：Arthritis Research and Therapy, 2014, 16(5): 472.

DOI：10.1186/s13075-014-0472-6

• COLLAGEN-INDUCED-ARTHRITIS
• SYNOVIAL FIBROBLASTS
• AMERICAN-COLLEGE
• GROWTH-FACTOR
• B ACTIVATION
• TNF-ALPHA
• EXPRESSION
• CELLS
• INFLAMMATION
• TISSUE

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction and disability. Peroxisorue proliferator activated receptor gamma coactivator 1beta (PCJC-1 beta) is a transcriptional coactivator that plays important roles in regulating multiple aspects of energy metabolism and cytokine signaling pathways. PGC-1 beta overexpression leads to the attenuation of macrophage -mediated inflammation. In this study, vve aimed to determine the expression of PGC-1 beta in RA synovium and fibroblast like synoviocytes (ELS), and explore the mechanisms of PGC-1 beta on both the proinflamruatory effects and apoptosis in RA FLS. @@@ Methods: Synovium \vas obtained from 31 patients with active RA, as well as 13 osteoarthritis (OA) and 10 orthopedic arthropathies (Orth.A) as "less inflamed" disease controls. ELS were then isolated and cultured. Synovial PGC-1 beta expression was determined by immunohistochemistry staining, while ELS PGC-1 beta expression was detected by immunofluorescence staining, quantitative real-time PCR (gPCR) assay and western blot PGC-1 beta was depleted by lentivirus sh-RNA, and up -regulated by pcDNA3.1- ()GC -1(3. The expression of proinflammatory cytokines, matrix metalloproteinases and receptor activator of nuclear factor-kappaB ligand was analyzed by OCR, cytometric bead array and western blot. The expression of mitogen-activated protein kinases and nuclear factor-kappaB (N KB) was determined by ciPCR and western blot. Besides, cell apoptosis was examined using flow cytometry. The interaction between PGC-1 beta and NE-KB was performed by dual-luciferase reporter gene assays. @@@ Results: (A) Synovial PGC-1 beta was over expressed in RA patients compared with OA or Orth.A patients. (B) PGC-1 beta expression significantly increased in RA-ELS compared with OA-ELS. (C) PGC-1 beta mediated the expression of proinflammatory cytokines and apoptosis through extracellular signal regulated kinase (ERK), p38 and NE-KB n RA-ELS. (D) PGC-1 beta mediated NE-KB transcription in RA-ELS, but did not affect ERK and p38. @@@ Conclusion: The results indicate that PGC-1 beta may play important roles in the proinflammatory effects arid apoptosis of RA-ELS.

• 出版日期2014
• 单位中山大学