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- 2018
Mongersen在牙周炎症微环境中抗炎作用的体外研究
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Abstract:
摘要 目的: 探讨Smad7反义寡核苷酸mongersen的体外抗炎作用。方法: 使用LipofectamineTM,2000载mongersen转染小鼠巨噬细胞RAW264.7,之后将RAW264.7与牙周炎的主要致病菌牙龈卟啉单胞菌的脂多糖(Porphyromonas gingivlis lipopolysaccharide,Pg-LPS)共培养,以模拟牙周炎症微环境,共培养12 h后,采用流式细胞术、Western blot、qRT-PCR分别检测转染效率、Smad7蛋白的表达情况及巨噬细胞相关细胞因子的表达。结果: 流式细胞术检测转染效率可达76.57%;Western blot结果显示mongersen可明显抑制Smad7蛋白的表达;qRT-PCR结果显示加入mongersen后肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)等促炎因子基因表达明显降低。结论: mongersen可通过抑制Smad7蛋白的表达发挥抗炎作用
[1] | Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation [J]. Nat Rev Immunol, 2015, 15(1)∶30-44 |
[2] | Maekawa T, Krauss JL, Abe T, et al. Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis [J]. Cell Host Microbe, 2014, 15(6)∶768-778 |
[3] | Benedyk M, Mydel PM, Delaleu N, et al. Gingipains: critical factors in the development of aspiration pneumonia caused by porphyromonas gingivalis [J]. J Innate Immun, 2016, 8(2)∶185-198 |
[4] | Monteleone G, Neurath MF, Ardizzone S, et al. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease [J]. N Engl J Med, 2015, 372(12)∶1104-1113 |
[5] | Marafini I, Di F, Calabrese E, et al. Antisense approach to inflammatory bowel disease: prospects and challenges [J]. Drugs, 2015, 75(7)∶723-730 |
[6] | Danese S, Fiorino G, Peyrin-Biroulet L. Targeting SMAD7 in Crohn's disease by Mongersen: therapeutic revolution under way [J]. Gastroenterology, 2015, 149(4)∶1121-1123 |
[7] | Chen W, Ten Dijke P. Immunoregulation by members of the TGF-β superfamily [J]. Nat Rev Immunol,2016,16(12)∶723-740 |
[8] | Lim R, Barker G, Lappas M. SMAD7 regulates proinflammatory and prolabor mediators in amnion and myometrium [J]. Biol Reprod, 2017, 97(2)∶288-301 |
[9] | Lam RS, O'Brien-Simpson NM, Lenzo JC, et al. Macrophage depletion abates porphyromonas gingivalis-induced alveolar bone resorption in mice [J]. J Immunol, 2014, 193(5)∶2349-2362 |
[10] | MohanKumar K, Namachivayam K, Chapalamadugu KC, et al. Smad7 interrupts TGF-β signaling in intestinal macrophages and promotes inflammatory activation of these cells during necrotizing enterocolitis [J]. Pediatr Res, 2016, 79(6)∶951-961 |