Effects of All-Trans Retinoic Acid on the Optimization of Synovial Explant Induced by Tumor Necrosis Factor Alpha

被引:1
作者
Cai, Qiuying [1 ]
Lyu, Yulin [1 ]
Lyu, Fan [1 ]
Zhou, Mingming [2 ]
Lu, Kuiqing [1 ]
Tang, Xiaoyue [1 ]
Ren, Dongxia [1 ]
Bao, Qilin [1 ]
Wang, Dan [1 ]
Li, Yun [1 ,3 ,4 ]
机构
[1] Sichuan Univ, West China Sch Publ Hlth, Dept Nutr Food Hyg & Toxicol, 17 Renmin South Rd, Chengdu 610041, Sichuan, Peoples R China
[2] Sichuan Univ, West China Hosp 2, Dept Clin Nutr, 20 Renmin South Rd, Chengdu 610041, Sichuan, Peoples R China
[3] Sichuan Univ, West China Sch Publ Hlth, 24 South Sect One,First Ring Rd, Chengdu 610065, Sichuan, Peoples R China
[4] Sichuan Univ, Hlth Food Evaluat Res Ctr, 24 South Sect One,First Ring Rd, Chengdu 610065, Sichuan, Peoples R China
基金
中国国家自然科学基金;
关键词
all-trans retinoic acid; rheumatoid arthritis; synovial explant; tumor necrosis factor alpha; immune inflammatory reaction; ENDOTHELIAL GROWTH-FACTOR; NF-KAPPA-B; RHEUMATOID-ARTHRITIS; EXPRESSION; INHIBITION; IL-6; INFLAMMATION; MODULATION; APOPTOSIS; AUTOPHAGY;
D O I
10.3177/jnsv.66.300
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Current studies focused on the effects of all-trans-retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were extracted aseptically from the quadriceps femoris of the knee joint of rats, and then incubated in medium containing 10% neonate bovine serum for 24 h adaptive culture. We first measured variations of correlation factors in synovium at 24, 48, 72, 96 and 120 h in control medium or in medium containing 20 ng/mL tumor necrosis factor alpha (TNF-alpha) (TNF-alpha-experiment). Then, we investigated the synovium exposed to three ATRA concentrations after 48 h incubation (ATRA-experiment). The effects of ATRA on synovitis were evaluated by observing the expression of inflammatory cytokines, angiogenic factors and the production of proteases in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) pathway and apoptosis and autophagy. In TNF-alpha-experiment, the secretion of nitric oxide (NO), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) increased significantly after TNF-alpha stimulation without pathological damage to the synovium. Hence, we successfully obtained the synovial explants model, which had longer inflammatory response time. In the ATRA-experiment, ATRA suppressed the secretion of IL-6 and NO, downregulated the NF-kappa B P65 and Bcl-2, increased levels of autophagy marker protein LC3, but different doses of ATRA showed inconsistent regulatory effects on VEGF and MMP-9. In short, ATRA inhibited TNF-alpha induced synovitis by the regulation of inflammatory cytokines and inhibiting NF-kappa B signal transduction and potentially promoting autophagy, apoptosis and angiogenesis, displaying its role in alleviating synovial inflammation in patients with RA.
引用
收藏
页码:300 / 310
页数:11
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