黑素瘤缺乏因子2(absent in melanoma2,AIM2)是一种主要定位于细胞质的蛋白质,其N端含有热蛋白(pyrin)结构域(PYD),而在C端为寡核苷酸/寡糖结合结构域。当AIM2与细胞质双链DNA结合后,它通过PYD相互作用而招募另一个细胞质蛋白质ASC,并...黑素瘤缺乏因子2(absent in melanoma2,AIM2)是一种主要定位于细胞质的蛋白质,其N端含有热蛋白(pyrin)结构域(PYD),而在C端为寡核苷酸/寡糖结合结构域。当AIM2与细胞质双链DNA结合后,它通过PYD相互作用而招募另一个细胞质蛋白质ASC,并诱导了炎性体的组装,从而引起随后胱天蛋白酶1(caspase-1)的激活和IL-1β的产生,诱导先天免疫反应甚至导致pyroptosis样细胞死亡。AIM2作为细胞质双链DNA感应蛋白的研究对先天免疫系统的理解和自身免疫性疾病(如系统性红斑狼疮等)的新治疗药物的设计具有重要意义。展开更多
1.Hiroko Tabunoki,Hidemasa Bono,Katsuhiko Ito,Takeshi Yokoyama。Can the silkworm（Bombyx mori）be used as a human disease model？Drug Discoveries＆Therapeutics.2016;10（1）：3-8.[题目]家蚕能被用作人类疾病模型吗？[摘要...1.Hiroko Tabunoki,Hidemasa Bono,Katsuhiko Ito,Takeshi Yokoyama。Can the silkworm（Bombyx mori）be used as a human disease model？Drug Discoveries＆Therapeutics.2016;10（1）：3-8.[题目]家蚕能被用作人类疾病模型吗？[摘要]在日本,家蚕是一种家喻户晓的鳞翅目昆虫,长期以来应用于纺织业,还是一种农业研究的模式昆虫。近年来,家蚕常被用于疾病分析的动物模型,展开更多
The role of the adaptive immune response, with regard to the development of autoantibodies, has been extensively studied in primary biliary cirrhosis (PBC). However, the importance of innate immunity has been noted on...The role of the adaptive immune response, with regard to the development of autoantibodies, has been extensively studied in primary biliary cirrhosis (PBC). However, the importance of innate immunity has been noted only recently. Based on the proposed role of microorganisms in the pathogenesis of the disease, we hypothesize that patients with PBC possess a hyper-responsive innate immune system to pathogen-associated stimuli that may facilitate the loss of tolerance. To address this issue, we isolated peripheral blood monocytes from 33 patients with PBC and 26 age-matched healthy controls and stimulated such cells in vitro with defined ligands for toll-like receptor (TLR) 2 (lipoteichoic acid; LTA), TLR3 (polyIC), TLR4 (lipopolysaccharide; LPS), TLR5 (flagellin), and TLR9 (CpG-B). Supernatant fluids from the cultures were analyzed for levels of 5 different pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, IL-8, IL-12p70, and TNF-α. After in vitro challenge with TLR ligands, PBC monocytes produced higher relative levels of pro-inflammatory cytokines, particularly IL-1β, IL-6, IL-8, and TNF-α, compared with controls. In conclusion, monocytes from patients with PBC appear more sensitive to signaling via select TLRs, resulting in secretion of selective pro-inflammatory cytokines integral to the inflammatory response that may be critical in the breakdown of self-tolerance.展开更多
文摘黑素瘤缺乏因子2(absent in melanoma2,AIM2)是一种主要定位于细胞质的蛋白质,其N端含有热蛋白(pyrin)结构域(PYD),而在C端为寡核苷酸/寡糖结合结构域。当AIM2与细胞质双链DNA结合后,它通过PYD相互作用而招募另一个细胞质蛋白质ASC,并诱导了炎性体的组装,从而引起随后胱天蛋白酶1(caspase-1)的激活和IL-1β的产生,诱导先天免疫反应甚至导致pyroptosis样细胞死亡。AIM2作为细胞质双链DNA感应蛋白的研究对先天免疫系统的理解和自身免疫性疾病(如系统性红斑狼疮等)的新治疗药物的设计具有重要意义。
文摘1.Hiroko Tabunoki,Hidemasa Bono,Katsuhiko Ito,Takeshi Yokoyama。Can the silkworm（Bombyx mori）be used as a human disease model？Drug Discoveries＆Therapeutics.2016;10（1）：3-8.[题目]家蚕能被用作人类疾病模型吗？[摘要]在日本,家蚕是一种家喻户晓的鳞翅目昆虫,长期以来应用于纺织业,还是一种农业研究的模式昆虫。近年来,家蚕常被用于疾病分析的动物模型,
文摘The role of the adaptive immune response, with regard to the development of autoantibodies, has been extensively studied in primary biliary cirrhosis (PBC). However, the importance of innate immunity has been noted only recently. Based on the proposed role of microorganisms in the pathogenesis of the disease, we hypothesize that patients with PBC possess a hyper-responsive innate immune system to pathogen-associated stimuli that may facilitate the loss of tolerance. To address this issue, we isolated peripheral blood monocytes from 33 patients with PBC and 26 age-matched healthy controls and stimulated such cells in vitro with defined ligands for toll-like receptor (TLR) 2 (lipoteichoic acid; LTA), TLR3 (polyIC), TLR4 (lipopolysaccharide; LPS), TLR5 (flagellin), and TLR9 (CpG-B). Supernatant fluids from the cultures were analyzed for levels of 5 different pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, IL-8, IL-12p70, and TNF-α. After in vitro challenge with TLR ligands, PBC monocytes produced higher relative levels of pro-inflammatory cytokines, particularly IL-1β, IL-6, IL-8, and TNF-α, compared with controls. In conclusion, monocytes from patients with PBC appear more sensitive to signaling via select TLRs, resulting in secretion of selective pro-inflammatory cytokines integral to the inflammatory response that may be critical in the breakdown of self-tolerance.
