AIM: To investigate the inhibitory effects and mechanism of high mobility group box(HMGB)1 A-box in lipopolysaccharide(LPS)-induced intestinal inflammation.METHODS: Overexpression of HMGB1 A-box in human intestinal ep...AIM: To investigate the inhibitory effects and mechanism of high mobility group box(HMGB)1 A-box in lipopolysaccharide(LPS)-induced intestinal inflammation.METHODS: Overexpression of HMGB1 A-box in human intestinal epithelial cell lines(SW480 cells) was achieved using the plasmid p EGFP-N1. HMGB1 A-box-overexpressing SW480 cells were stimulated with LPS and co-culturing with human monocyte-like cell lines(THP-1 cells) using a Transwell system, compared with another HMGB1 inhibitor ethyl pyruvate(EP). The m RNA and protein levels of HMGB1/toll-like receptor(TLR) 4 signaling pathways [including HMGB1, TLR4, myeloid differentiation factor88(MYD88), Phosphorylated Nuclear Factor κB(p NF-κB) p65] in the stimulated cells were determined by realtime polymerase chain reaction and Western blotting. The levels of the proinflammatory mediators [including HMGB1, interleukin(IL)-1β, IL-6 and tumor necrosis factor(TNF)-α] in the supernatants of the stimulated cells were determined by ELISA.RESULTS: EP downregulated the m RNA and protein levels of HMGB1, inhibited the TLR4 signaling pathways(TLR4, MYD88 and p NF-κB p65) and reduced the secretion of proinflammatory mediators(HMGB1, IL-1β, IL-6 and TNF-α) in the SW480 and THP-1 cells activated by LPS but not in the unstimulated cells. Activated by LPS, the overexpression of HMGB1 A-box in the SW480 cells also inhibited the HMGB1/TLR4 signaling pathways and reduced the secretion of these proinflammatory mediators in the THP-1 cells but not in the transfected and unstimulated cells. CONCLUSION: HMGB1 A-box, not only EP, can reduce LPS-induced intestinal inflammation through inhibition of the HMGB1/TLR4 signaling pathways.展开更多
哺乳动物高迁移率族蛋白(high mobility group box,HMGB)是一种含有两个串联的HMG box为主要特征的非组蛋白染色体DNA结合蛋白.HMGB参与许多生物学过程,包括染色质重塑、基因复制与转录调控、DNA修复等,包含细胞发育与免疫方面的许多功...哺乳动物高迁移率族蛋白(high mobility group box,HMGB)是一种含有两个串联的HMG box为主要特征的非组蛋白染色体DNA结合蛋白.HMGB参与许多生物学过程,包括染色质重塑、基因复制与转录调控、DNA修复等,包含细胞发育与免疫方面的许多功能.分析不同物种的HMGB基因,发现高等物种中的HMGB基因起源于古老的无内含子的单一外显子基因,这个单一外显子的基因会随着演化的进行而获得不同数目的内含子.经典的HMGB蛋白在多细胞生物和单细胞原生生物中非常保守,它起源于单一外显子编码的DNA结合结构域基因的复制与融合.展开更多
感染是导致早产的主要环境因素之一。警报素(alarmin)概念的提出至今不足10年,但已逐渐显示出其在调节感染相关的免疫反应中所起的关键作用。高迁移率族蛋白B1(high-mobility group box-1,HMGB1)是一个多功能的警报素,参与了多种疾病的...感染是导致早产的主要环境因素之一。警报素(alarmin)概念的提出至今不足10年,但已逐渐显示出其在调节感染相关的免疫反应中所起的关键作用。高迁移率族蛋白B1(high-mobility group box-1,HMGB1)是一个多功能的警报素,参与了多种疾病的发生发展,包括感染性疾病。近年研究显示HMGB1可通过其受体Toll样受体4(toll-like receptor 4,TLR4)和晚期糖基化终产物受体(receptor for advanced glycation end products,RAGE)参与感染所致早产的发生和发展。根据该领域最新进展,依次综述了HMGB1、TLR4、RAGE以及后两者各自的可溶性形式在早产中的作用和意义,指出TLR4介导的急性炎症与RAGE介导的慢性炎症可能在早产的发生发展过程中共同发挥作用,HMGB1及其受体的可溶性形式有望成为简便、高效的早产相关的生物标记物。展开更多
文摘目的观察脑缺血后HMGB1/TLR4/NF-κB的表达变化,探讨木犀草素的干预研究。方法用改良线栓法制作大鼠大脑中动脉闭塞(MCAO)模型。梗死后腹腔内立即注射木犀草素,在梗死后24h采用Western blot和RT-qPCR观察HMGB1/TLR4/NF-κB蛋白和基因表达变化。结果脑梗死后24 h HMGB1/TLR4/NF-κB的表达明显上调(P<0.05)。木犀草素低剂量组下调HMGB1/TLR4/NF-κB的表达不明显(P>0.05)。木犀草素高剂量组下调TLR4/NF-κB的表达明显(P<0.05)。木犀草素可能是通过抑制HMGB1/TLR4/NF-κB的表达起到脑保护作用。结论 HMGB1/TLR4/NF-κB可能是木犀草素的靶点之一,木犀草素可能是通过抑制HMGB1/TLR4/NF-κB的表达发挥其脑保护的作用。
基金Supported by National Natural Science Foundation of China,No.81160056the Youth Science Foundation of Jiangxi Provincial,China,No.20132BAB215017
文摘AIM: To investigate the inhibitory effects and mechanism of high mobility group box(HMGB)1 A-box in lipopolysaccharide(LPS)-induced intestinal inflammation.METHODS: Overexpression of HMGB1 A-box in human intestinal epithelial cell lines(SW480 cells) was achieved using the plasmid p EGFP-N1. HMGB1 A-box-overexpressing SW480 cells were stimulated with LPS and co-culturing with human monocyte-like cell lines(THP-1 cells) using a Transwell system, compared with another HMGB1 inhibitor ethyl pyruvate(EP). The m RNA and protein levels of HMGB1/toll-like receptor(TLR) 4 signaling pathways [including HMGB1, TLR4, myeloid differentiation factor88(MYD88), Phosphorylated Nuclear Factor κB(p NF-κB) p65] in the stimulated cells were determined by realtime polymerase chain reaction and Western blotting. The levels of the proinflammatory mediators [including HMGB1, interleukin(IL)-1β, IL-6 and tumor necrosis factor(TNF)-α] in the supernatants of the stimulated cells were determined by ELISA.RESULTS: EP downregulated the m RNA and protein levels of HMGB1, inhibited the TLR4 signaling pathways(TLR4, MYD88 and p NF-κB p65) and reduced the secretion of proinflammatory mediators(HMGB1, IL-1β, IL-6 and TNF-α) in the SW480 and THP-1 cells activated by LPS but not in the unstimulated cells. Activated by LPS, the overexpression of HMGB1 A-box in the SW480 cells also inhibited the HMGB1/TLR4 signaling pathways and reduced the secretion of these proinflammatory mediators in the THP-1 cells but not in the transfected and unstimulated cells. CONCLUSION: HMGB1 A-box, not only EP, can reduce LPS-induced intestinal inflammation through inhibition of the HMGB1/TLR4 signaling pathways.
文摘哺乳动物高迁移率族蛋白(high mobility group box,HMGB)是一种含有两个串联的HMG box为主要特征的非组蛋白染色体DNA结合蛋白.HMGB参与许多生物学过程,包括染色质重塑、基因复制与转录调控、DNA修复等,包含细胞发育与免疫方面的许多功能.分析不同物种的HMGB基因,发现高等物种中的HMGB基因起源于古老的无内含子的单一外显子基因,这个单一外显子的基因会随着演化的进行而获得不同数目的内含子.经典的HMGB蛋白在多细胞生物和单细胞原生生物中非常保守,它起源于单一外显子编码的DNA结合结构域基因的复制与融合.
文摘感染是导致早产的主要环境因素之一。警报素(alarmin)概念的提出至今不足10年,但已逐渐显示出其在调节感染相关的免疫反应中所起的关键作用。高迁移率族蛋白B1(high-mobility group box-1,HMGB1)是一个多功能的警报素,参与了多种疾病的发生发展,包括感染性疾病。近年研究显示HMGB1可通过其受体Toll样受体4(toll-like receptor 4,TLR4)和晚期糖基化终产物受体(receptor for advanced glycation end products,RAGE)参与感染所致早产的发生和发展。根据该领域最新进展,依次综述了HMGB1、TLR4、RAGE以及后两者各自的可溶性形式在早产中的作用和意义,指出TLR4介导的急性炎症与RAGE介导的慢性炎症可能在早产的发生发展过程中共同发挥作用,HMGB1及其受体的可溶性形式有望成为简便、高效的早产相关的生物标记物。
